生物機能ならびに生物材料を利用した高性能イオン交換材料の開発に関して、これまで発表した４００編以上の業績が認められ、日本イオン交換学会の学会賞が授与された。

記述言語：その他   掲載種別：研究論文（学術雑誌）   出版者・発行元：ChemBioEng Reviews  

Despite advances in cancer treatment, many types of cancer still have high mortality rates, and the existing therapies can cause considerable side effects. Therefore, discovering new therapies, especially ones with fewer side effects, is desirable to improve the outcomes for cancer patients. Ionic liquids (ILs) have emerged as potential candidates for cancer treatment because of their particular physicochemical properties, which can be tailored for specific applications. In recent years, interest in exploring the potential of ILs in cancer treatment has been growing, and several studies have demonstrated the effectiveness of ILs in inhibiting cancer-cell growth. This review provides insight into the anticancer potential of ILs, exploring the diverse applications and the underlying mechanisms behind the cytotoxicity toward cancer cells of ILs. Understanding the mechanisms behind the cytotoxicity of ILs can aid in the design and optimization of IL-based cancer therapies. By focusing on specific pathways and targets, IL-based cancer therapies may be developed that offer new possibilities for treating this devastating disease.

DOI： 10.1002/cben.202300051

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記述言語：その他   掲載種別：研究論文（学術雑誌）   出版者・発行元：Food Chemistry  

Flavonoids have diverse beneficial roles that potentiate their application as nutraceutical agents in nutritional supplements and as natural antimicrobial agents in food preservation. To address poor solubility and bioactivity issues, we developed water-soluble micellar formulations loaded with single and multiple flavonoids using the biocompatible surface-active ionic liquid choline oleate. The food preservation performance was investigated using luteolin, naringenin, and quercetin as model bioactive compounds. The micellar formulations formed spherical micelles with particle sizes of <150 nm and exhibited high aqueous solubility (>5.15 mg/mL). Co-delivery of multiple flavonoids (luteolin, naringenin, and quercetin in LNQ-MF) resulted in 84.85% antioxidant activity at 100 μg/mL. The effects on Staphylococcus aureus and Salmonella enterica were synergistic with fractional inhibitory concentration indices of 0.87 and 0.71, respectively. LNQ-MF hindered the growth of S. aureus in milk (0.83–0.89 log scale) compared to the control. Co-delivered encapsulated flavonoids are a promising alternative to chemical preservatives.

DOI： 10.1016/j.foodchem.2023.136911

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記述言語：その他   掲載種別：研究論文（学術雑誌）  

DOI： 10.21203/rs.3.rs-3338523/v1

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記述言語：その他   掲載種別：研究論文（学術雑誌）   出版者・発行元：Chemical Record  

Ionic liquids (ILs) have been extensively used in drug formulation and delivery as designer solvents and other components because of their inherent tunability and useful physicochemical and biopharmaceutical properties. ILs can be used to manage some of the operational and functional challenges of drug delivery, including drug solubility, permeability, formulation instability, and in vivo systemic toxicity, that are associated with conventional organic solvents/agents. Furthermore, ILs have been recognized as potential solvents to address the polymorphism, limited solubility, poor permeability, instability, and low bioavailability of crystalline drugs. In this account, we discuss the technological progress and strategies toward designing biocompatible ILs and explore potential biomedical applications, namely the solubilization of small and macromolecular drugs, the creation of active pharmaceutical ingredients, and the delivery of pharmaceuticals.

DOI： 10.1002/tcr.202300026

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記述言語：その他   掲載種別：研究論文（学術雑誌）   出版者・発行元：ACS Applied Materials and Interfaces  

Nucleic acid drugs, including antisense oligonucleotides (ASOs), have received considerable attention as novel therapeutics for the treatment of intractable diseases. Despite their potential benefits, ASOs are currently administered via injection, which can negatively impact patient quality of life because of the prevalence of severe injection site reactions. Non-invasive transdermal administration of ASOs is desirable but highly challenging owing to the strong barrier imposed by the stratum corneum, which only permits the penetration of small molecules under 500 Da. For ASOs to exert their antisense effect, they must traverse the negatively charged cell membrane and reach the cytoplasm. In this study, we used the solid-in-oil (S/O) dispersion technology to facilitate the skin permeation of ASOs by coating the drug with a hydrophobic surfactant molecule, specifically lipid-based ionic liquid (IL) surfactants with high biocompatibility and transdermal penetration-enhancing properties. To induce the antisense effect, it was important to achieve simultaneous transdermal delivery and intracellular entrapment of ASOs. In vitro investigations indicated that the newly prepared IL-S/O enhanced the transdermal penetration and intracellular delivery of ASOs, thus inhibiting mRNA translation of the target TGF-β. In addition, in vivo investigations of tumor-bearing mice suggested that the anti-tumor effect of the IL-S/O was similar to that of injection. This study demonstrates the potential of non-invasive transdermal delivery carriers based on biocompatible ILs, which can be applied to a variety of nucleic acid drugs.

DOI： 10.1021/acsami.3c03900

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：日本溶媒抽出学会  

Recycling platinum group metals from secondary resources such as spent automotive exhaust catalysts is promising for the circular economy. However, the selective separation of Pt over massive amounts of impurity metals such as Mg and Al is particularly challenging. In this study, non-aqueous direct leaching of platinum from a spent automotive catalyst (SAC) using hydrophobic ionic liquids, namely, trihexyl(tetradecyl)phosphonium chloride (P66614Cl) and trioctyl(dodecyl)phosphonium chloride (P88812Cl) with the aid of pre-loading hydrochloric acid/hydrogen peroxide was proposed. The more hydrophobic P88812Cl exhibited more efficient and selective leaching of Pt over Mg and Al. The recovery of Pt from the metal-loaded P88812Cl, and the reusability of the IL for SAC leaching were also demonstrated.

DOI： 10.15261/serdj.30.149

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Processes  

The current alternative of using aromatic-based wax soak solvents has been found to be hazardous and imposes a high cost on field expenditures. These solvents are widely used in the oil and gas industry to soften up wax before the pigging process. However, their impacts on the environment are quite concerning. Plus, they also impose hazardous exposure and are found to be damaging to both plastic and rubber hoses. To replace the current alternative with other hydrocarbon-based wax soak solvents, ionic liquids were found to have the capability to increase the solvent power capabilities and the efficiency of wax soak solvent in dissolving heavy crude oil. To optimise the application of hydrocarbon solvents and ionic liquid in wax dissolution, the affinity of ionic liquids in three solvents was studied. The solvents were condensate, ethyl acetate, and xylene. It was found that from four types of ionic liquids tested, only BMIMCL and HMIMBr were miscible in all three of the solvents used. Dissolution of hard deposited paraffin wax in condensate, ethyl acetate and xylene was conducted using the spectral analysis method, and it was found that the dissolution of paraffin wax was greatest in ethyl acetate. However, enchantment on wax dissolution was also observed for gas condensate and xylene. The wax soaking time was also optimised, in which the dissolution of wax was found to reach a saturation level when the wax had been soaked for over 90 min in the solvents, especially for gas condensate. Further study on the effect of ionic liquid introduced alongside condensate, ethyl acetate and xylene, aiming to enhance the solvent power, was also conducted using the spectral analysis method. The introduction of ionic liquids to all hydrocarbon-based wax soak solvents used in this project was proven to significantly increase the UV-VIS absorbance of the extracted solvents after paraffin wax had been soaked for 30 min.

DOI： 10.3390/pr11041112

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記述言語：その他  

DOI： 10.3390/molecules28072969

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Molecules  

Ibuprofen (Ibf) is a biologically active drug (BADs) and an emerging contaminant of concern (CECs) in aqueous streams. Due to its adverse effects upon aquatic organisms and humans, the removal and recovery of Ibf are essential. Usually, conventional solvents are employed for the separation and recovery of ibuprofen. Due to environmental limitations, alternative green extracting agents need to be explored. Ionic liquids (ILs), emerging and greener alternatives, can also serve this purpose. It is essential to explore ILs that are effective for recovering ibuprofen, among millions of ILs. The conductor-like screening model for real solvents (COSMO-RS) is an efficient tool that can be used to screen ILs specifically for ibuprofen extraction. The main objective of this work was to identify the best IL for the extraction of ibuprofen. A total of 152 different cation?anion combinations consisting of eight aromatic and non-aromatic cations and nineteen anions were screened. The evaluation was based upon activity coefficients, capacity, and selectivity values. Furthermore, the effect of alkyl chain length was studied. The results suggest that quaternary ammonium (cation) and sulfate (anion) have better extraction ability for ibuprofen than the other combinations tested. An ionic liquid-based green emulsion liquid membrane (ILGELM) was developed using the selected ionic liquid as the extractant, sunflower oil as the diluent, Span 80 as the surfactant, and NaOH as the stripping agent. Experimental verification was carried out using the ILGELM. The experimental results indicated that the predicted COSMO-RS and the experimental results were in good agreement. The proposed IL-based GELM is highly effective for the removal and recovery of ibuprofen.

DOI： 10.3390/molecules28052345

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Hydrometallurgy  

Solvent extraction of scandium(III) from an aqueous solution, which simulates a concentrated scandium solution generated from nickel/cobalt mixed-sulfide production process, was performed using a ternary mixed extractant system. Addition of tri-n-octylphosphine oxide and a long-chain alkyl carboxylic acid (Versatic 10) to an organophosphonic ester (PC-88A) drastically improved the separation factor of scandium over zirconium in comparison with that of a single extractant system. The optimum mixing ratio in the ternary extractant system was 10 mol% PC-88A, 60 mol% tri-n-octylphosphine oxide, and 30 mol% Versatic 10. The degree of scandium extraction was 90%, and the separation factors between scandium and other metals (i.e., Al, Fe, Ni, Cr, and Zr) were > 140 at pH 2 with the optimized ternary extractant system. The operating conditions for a countercurrent multistage extraction of scandium were investigated by McCabe?Thiele analysis. Ninety-nine percent recovery from 1800 mg dm?3 scandium was achieved by two- to three-stage countercurrent extraction at the flow ratio (A/O) = 1.01. The stripping efficiency of scandium reached >98% with 7 mol dm?3 H3PO4. Based on the results, a conceptual flowsheet for scandium recovery from waste solutions of laterite ore leachate is proposed.

DOI： 10.1016/j.hydromet.2023.106024

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記述言語：その他   掲載種別：研究論文（学術雑誌）   出版者・発行元：Pharmaceutics  

The development of effective drug formulations and delivery systems for newly developed or marketed drug molecules remains a significant challenge. These drugs can exhibit polymorphic conversion, poor bioavailability, and systemic toxicity, and can be difficult to formulate with traditional organic solvents due to acute toxicity. Ionic liquids (ILs) are recognized as solvents that can improve the pharmacokinetic and pharmacodynamic properties of drugs. ILs can address the operational/functional challenges associated with traditional organic solvents. However, many ILs are non-biodegradable and inherently toxic, which is the most significant challenge in developing IL-based drug formulations and delivery systems. Biocompatible ILs comprising biocompatible cations and anions mainly derived from bio-renewable sources are considered a green alternative to both conventional ILs and organic/inorganic solvents. This review covers the technologies and strategies developed to design biocompatible ILs, focusing on the design of biocompatible IL-based drug formulations and delivery systems, and discusses the advantages of these ILs in pharmaceutical and biomedical applications. Furthermore, this review will provide guidance on transitioning to biocompatible ILs rather than commonly used toxic ILs and organic solvents in fields ranging from chemical synthesis to pharmaceutics.

DOI： 10.3390/pharmaceutics15041179

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記述言語：その他   掲載種別：研究論文（学術雑誌）  

Transcutaneous vaccination is one of the successful, affordable, and patient-friendly advanced immunization approaches because of the presence of multiple immune-responsive cell types in the skin. However, in the absence of a preferable facilitator, the skin’s outer layer is a strong impediment to delivering biologically active foreign particles. Lipid-based biocompatible ionic-liquid-mediated nanodrug carriers represent an expedient and distinct strategy to permit transdermal drug delivery; with acceptable surfactants, the performance of drug formulations might be further enhanced. For this purpose, we formulated a lipid-based nanovaccine using a conventional (cationic/anionic/nonionic) surfactant loaded with an antigenic protein and immunomodulator in its core to promote drug delivery by penetrating the skin and boosting drug delivery and immunogenic cell activity. In a follow-up investigation, a freeze–dry emulsification process was used to prepare the nanovaccine, and its transdermal delivery, pharmacokinetic parameters, and ability to activate autoimmune cells in the tumor microenvironment were studied in a tumor-budding C57BL/6N mouse model. These analyses were performed using ELISA, nuclei and HE staining, flow cytometry, and other biological techniques. The immunomodulator-containing nanovaccine significantly (p < 0.001) increased transdermal drug delivery and anticancer immune responses (IgG, IgG1, IgG2, CD8+, CD207+, and CD103+ expression) without causing cellular or biological toxicity. Using a nanovaccination approach, it is possible to create a more targeted and efficient delivery system for cancer antigens, thereby stimulating a stronger immune response compared with conventional aqueous formulations. This might lead to more effective therapeutic and preventative outcomes for patients with cancer.

DOI： 10.3390/molecules28072969

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Journal of Pharmaceutical Sciences  

Malaria is a mosquito-borne infectious disease that is widespread in developing countries. Malaria vaccines are important in efforts to eradicate malaria; however, vaccines are usually administered by injection, which requires medical personnel and has a risk of causing infection. Transdermal vaccines can be administered without damaging the skin and thus are ideal for the prevention of malaria. However, the stratum corneum forms a "brick and mortar" like structure in which stratum corneum cells are embedded in a hydrophobic matrix composed of lipids, which strongly inhibits the permeation of hydrophilic substances. In the present study, we designed a transdermal vaccine against vivax malaria using a solid-in-oil (S/O) dispersion. The S/O dispersion of a transmission blocking vaccine candidate, Pvs25 from Plasmodium vivax, showed higher skin penetration than that of the aqueous solution. Mice immunized with the S/O dispersion generated antibodies at similar titers as the mice immunized by injection, over the mid- to long-term. These results provide information for the development of transdermally administered malaria vaccines toward the eradication of malaria.

DOI： 10.1016/j.xphs.2022.10.031

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ACS Omega  

To reduce the exploitation of mine resources and decrease the harm to the environment caused by urban electronic wastes, the recovery of critical metals in secondary resources is crucial. In this study, we have successfully developed an eco-friendly process to integrate the leaching and separation of cobalt (Co) from a spent lithium-ion battery (LIB) cathode using an amino acid-based aqueous biphasic system (ABS). We, for the first time, demonstrated a simple method for leaching a LIB cathode using only amino acids. In addition, we have investigated the leaching mechanism using the typical cathode active material lithium cobalt oxide (LiCoO2). Then, the Co was selectively extracted by a biphasic system (amino acid?PPG400?H2O). This novel process has an excellent prospect in the field of spent-battery recycling because of its eco-friendly and process-simplified advantages.

DOI： 10.1021/acsomega.2c06654

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ACS Applied Materials and Interfaces  

The transdermal delivery of hydrophilic drugs remains challenging owing to their poor ability to permeate the skin; formulation with oil media is difficult without adding chemical permeation enhancers or co-solvents. Herein, we synthesized 12 oil-miscible ionic liquid (IL) drugs comprising lidocaine-, imipramine-, and levamisole (Lev)-hydrochloride with fatty acid permeation enhancers, i.e., laurate, oleate, linoleate, and stearate as counterions. A set of in vitro and in vivo studies was performed to investigate the potency and deliverability of the transdermal drug formulations. All of the synthesized compounds were freely miscible with pharmaceutically acceptable solvents/agents (i.e., ethanol, N-methyl pyrrolidone, Tween 20, and isopropyl myristate (IPM)). In vitro permeation studies revealed that the oleate-based Lev formulation had 2.6-fold higher skin permeation capability than the Lev salts and also superior ability compared with the laurate-, linoleate-, and stearate-containing samples. Upon in vivo transdermal administration to mice, the peak plasma concentration, elimination half-life, and area under the plasma concentration curve values of Lev-IL were 4.6-, 2.9-, and 5.4-fold higher, respectively, than those of the Lev salt. Furthermore, in vitro skin irritation and in vivo histological studies have demonstrated that Lev-IL has excellent biocompatibility compared with a conventional ionic liquid-based carrier. The results indicate that oil-miscible IL-based drugs provide a simple and scalable strategy for the design of effective transdermal drug delivery systems.

DOI： 10.1021/acsami.2c15636

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Journal of Molecular Liquids  

Luteolin (LUT), an important flavonoid, shows excellent antioxidant and antimicrobial properties. However, its low solubility and stability in water, as well as challenges related to its formulation, have limited its use in food preservation. Here, we develop a highly water-soluble LUT-loaded micellar formulation (LUT-MF) using a solid-in-water nanodispersion technique involving emulsification and lyophilization processes. LUT solubilized in an organic phase comprising acetone, methanol, and cyclohexane (5:10:85 v/v) was emulsified with an aqueous solution of a surface-active ionic liquid, choline oleate ([Cho][Ole]), and the oil in water emulsion was lyophilized to remove the organic phase and water and obtain a solid LUT-[Cho][Ole] complex. LUT-[Cho][Ole] complex was dispersed again in water to prepare the LUT-MF formulation with good stability. Dynamic light scattering and transmission electron microscopy confirmed that the LUT-MF formed spherical micelles with a mean particle size of approximately 73 nm. LUT-MF showed excellent encapsulation efficiency (94.3%) and enhanced aqueous solubility. An in vitro release study in PBS containing 30% ethanol demonstrated 3.94 times higher release of LUT from LUT-MF than from LUT suspension after 24 h. The developed formulation showed better antioxidant activity than both free LUT and ascorbic acid. LUT-MF demonstrated higher antibacterial activity than sodium benzoate. Food preservation studies revealed that treating strawberries with LUT-MF effectively preserved color and prevented shriveling and decay over 8 days storage at 10 °C, compared with sodium benzoate treatment. The results suggest that LUT-MF is a potential natural preservative alternative to conventional toxic chemical preservatives used in the food industry.

DOI： 10.1016/j.molliq.2022.120151

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記述言語：その他   掲載種別：研究論文（学術雑誌）   出版者・発行元：Biochemical Engineering Journal  

Selectivity is a crucial factor for gold recovery from discarded cell phones. This is because discarded cell phones contain a large variety of metals. The use of biomaterials as gold adsorbents is attracting much attention because it is in accordance with sustainability goals. Here, we reported selective adsorption of gold on silk fibroin and its application to gold recovery from the actual leachate of discarded cell phones in a chloride medium. The experimental maximum gold-adsorption capacity of silk fibroin was 5.800 mg/g. Based on a kinetic study, the gold-adsorption mechanism followed the pseudo-second-order model with a rate constant (k2) of 0.077 g mg−1min−1. The adsorption fitted well with the Langmuir model, suggesting a monolayer adsorption mechanism. Despite the small adsorption capacity, silk fibroin showed remarkable selectivity toward gold in synthetic and actual leachate containing Pt4+, Pd2+, Al3+, Cu2+, Ni2+, Zn2+, Pb2+, and Fe3+ metal ions in 0.5 mol/L HCl. The gold uptake from the actual leachate of discarded cell phones was approximately 95 %. The gold loaded on the silk fibroin was completely desorbed by 0.1 mol/L thiourea.

DOI： 10.1016/j.bej.2022.108690

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記述言語：その他   掲載種別：研究論文（学術雑誌）   出版者・発行元：ACS Sustainable Chemistry and Engineering  

Metals are key components of modern devices; however, available resources of these metals are limited. In this study, we used machine learning (ML) to curate ionic liquids (ILs) that are suitable for metal extraction. We proposed classification and regression models to unravel hidden patterns between IL structures and their specific properties, i.e., metal selectivity and eco-toxicity. Evaluations of ML models using cross-validation indicate that the models were reliable, as described by the accuracy score (0.82) and R2value (0.76). The models also revealed that the metal selectivity of ILs was determined by the cation and anion structures, and the eco-toxicity level was primarily affected by the cation structures. Guided by predictions from the trained models, we selected three ILs (out of the 150 IL structures we initially proposed) that have extraction selectivity toward platinum, lithium, and neodymium as well as low eco-toxicity. We then prepared the ILs in the laboratory and assessed their performance by standard solvent extraction. The experiments indicate that the recommended ILs from ML could selectively extract the targeted metals with high extraction efficiency (>80%), which demonstrates the feasibility of ML as a promising toolkit that can help accelerate innovations in metal extraction.

DOI： 10.1021/acssuschemeng.2c03480

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ACS Applied Bio Materials  

enhanced, and the transdermal distribution and transdermal flux of the OVA delivery system were 25 and 28 times greater, respectively, than those of its aqueous formulation. The PCNC disrupted the order of lipid orientation in the skin’s SC and increased intercellular protein delivery. It demonstrated effective antitumor activity, drastically (p < 0.001) suppressed tumor growth, increased mouse survival rates, and significantly (p < 0.001) stimulated the OVA-specific tumor immune response. The PCNC also increased the number of cytotoxic T cells expressing CD8 antibodies on their surfaces (CD8 + T-cells) in the tumor microenvironment. These findings suggest that PCNCs may be promising biocompatible carriers for transdermal antigenic protein delivery in tumor immunotherapy.

DOI： 10.1021/acsabm.2c00061

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Green Chemistry  

Expansion of the global market for electric vehicles has brought about a significant increase in the demand for the critical metals necessary for lithium-ion battery cathodes. Conventional cathode recycling processes can be detrimentally impactful to the environment because of the high-temperature treatment needed, and the hazardous inorganic acids and organic solvents used. Here, we demonstrate a novel cathode recycling process that employs hydrophobic eutectic solvents (HESs), which have recently attracted interest as green solvents. Our proposed process operates at mild temperatures and uses a reusable HES as an alternative to the aforementioned hazardous acids and solvents. This process consists of two simple steps, starting with direct leaching of the cathode materials by HESs typically composed of synergistic metal ligands, such as a diketone and an alkyl phosphine oxide, after which the leached critical metal ions are then separated and recovered into an aqueous oxalic acid solution. Under the optimal conditions, more than 90% of lithium, cobalt, and other critical metals was leached out from the various cathode materials, aided by ascorbic acid as the natural reducing agent. Subsequently, the metals were quantitatively recovered from the HES into the stripping solution as the cobalt oxalate precipitation and lithium-rich solution. We have succeeded in developing a potentially environmentally harmonious recycling process suitable for the sustainable production of rechargeable batteries.

DOI： 10.1039/D1GC04846E

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記述言語：その他   掲載種別：研究論文（学術雑誌）   出版者・発行元：Industrial and Engineering Chemistry Research  

The era of electric vehicles is rapidly approaching, and therefore, it is crucial to provide a sustainable technology for ensuring the circular economy of lithium-ion batteries. In this study, we report the development of a novel aqueous biphasic system (ABS) comprising fully biocompatible components, that is, hydrophilic ionic liquids, amino acids, and organic acids, for the selective recovery of Co(II) and Ni(II) from Mn(II), which are critical metals in spent lithium-ion batteries. Separation of Co(II), Ni(II), and Mn(II) from sulfate media was successfully carried out using the ABS in a quite straightforward manner without any hazardous reagents or organic solvents. In addition, the plausible mechanism of metal ion separation within the ABS was elucidated. The regenerated ionic liquid in the ABS exhibited remarkably stable performance during use in three consecutive experimental cycles.

DOI： 10.1021/acs.iecr.2c00295

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記述言語：その他   掲載種別：研究論文（学術雑誌）   出版者・発行元：Biomaterials  

The biomaterial-based immunoengineering has become one of the most attractive research fields in the last decade. In the present study, a solid-in-oil-in-water (S/O/W) emulsion encapsulating antigen in the oil phase of an oil-in-water (O/W) emulsion was prepared as a novel vaccine carrier consisting of similar materials to the emulsion adjuvant of which the safety, immunogenicity and vaccination efficacy have been already confirmed in human. Direct observation by high-resolution confocal laser scanning microscopy and small angle X-ray scattering analysis showed that the antigens were dispersed inside of the oil phase of the S/O/W emulsion as solid-state particles. The S/O/W emulsion robustly produced antigen-specific antibodies and enhanced the antitumor effects in a therapeutic cancer vaccination compared with free antigens or the O/W emulsion in vivo. This result is in good agreement with the activation effect of antigen-specific cytotoxic T lymphocytes and antigen presentation by the S/O/W emulsion, indicating that the S/O/W emulsion consisting of already approved materials is a promising vaccine carrier to produce both humoral and cellular immunity.

DOI： 10.1016/j.biomaterials.2022.121385

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Journal of Molecular Liquids  

Ionic liquids (ILs) have gained great attention as potent solubilizing agents of poorly soluble bioactive compounds. The use of Luteolin (LUT) – a natural bioactive compound – is limited because of its poor aqueous solubility. To address this issue, this study reports potential ILs for effectively solubilizing LUT at ambient temperature. First, promising ILs were screened from a potential 180 ILs that were proposed by the combination of 20 standard amino acid ethyl esters cations and nine phenolic acids anions using the conductor-like screening model for real solvents (COSMO-RS); the activity coefficients of LUT at infinite dilution in ILs were used as the screening criteria. Four proline ethyl ester phenolate ILs (PEEP-ILs) composed of a biocompatible proline ethyl ester and bioactive phenolic acids (trans-ferulic, vanillic, p-coumaric, and 4-hydroxybenzoic acid) were selected and synthesized. The synthesized PEEP-ILs were characterized through 1H NMR, FT-IR, elemental analysis, TGA, and DSC. The experimental solubility of LUT in PEEP-ILs (60% IL in water) showed excellent solubility. Among the PEEP-ILs, proline ethyl ester ferulate (IL[ProEt][Fer]) exhibited the best LUT solubility, followed by ILs with p-coumarate (IL[ProEt][Cou]), vanillate (IL[ProEt][Van]), and 4-hydroxybenzoate (IL[ProEt][Ben]). 1H NMR assessment and COSMO-RS prediction confirmed that the ILs facilitated the solubilization of LUT through multiple hydrogen bonding, π − π, and cation − π interactions between the LUT and the ILs. The biocompatibility study revealed that PEEP-ILs were relatively harmless and low toxicity compared with conventional imidazolium, pyridinium, pyrrolidinium, piperidinium, and morpholinium-based ILs. The LUT dissolved in the newly-synthesized PEEP-ILs and demonstrated better organoleptic properties on red apple slices. These results indicate that PEEP-ILs can be potential green alternatives to conventional toxic solvents for dissolving poorly water-soluble bioactive natural preservatives.

DOI： 10.1016/j.molliq.2021.118103

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Separation and Purification Technology  

To establish more efficient and environmentally friendly lithium-ion battery (LiB) recycling processes, novel extractants derived from amino acids that enable better separation of Ni and Co were explored using density functional theory (DFT) calculations. DFT calculations and experimental validation indicated that of the three coordination sites-namely amine, amide, and carboxyl groups in the amic-acid ligands-the bond strength of the central amine group to the metal determines the Ni and Co separation performance. Based on the findings, the glycine-derived amic-acid extractant N-[N,N-di(2-ethylhexyl)aminocarbonylmethyl]glycine (D2EHAG) was applied for the recovery of Ni and Co from a spent automotive LiB leachate. Preferential and mutual recovery of Ni and Co from manganese by the D2EHAG-based recycling process was demonstrated. This study provides insights into the design of extractants that enable the mutual separation of Ni, Co, and Mn, and indicates the suitability of amic-acid extractants for LiB recycling processes.

DOI： 10.1016/j.seppur.2021.119898

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Acta Biomaterialia  

Transcutaneous drug delivery is a promising method in terms of drug repositioning and reformulation because of its non-invasive and easy-to-use features. To overcome the skin barrier, which is the biggest challenge in transcutaneous drug delivery, a number of techniques, such as microemulsion, solid-in-oil dispersions and liposomes, have been studied extensively. However, the low viscosity of these formulations limits drug retention on the skin and reduces patient acceptability. Although viscosity can be increased by adding a thickening reagent, such an addition often alters formulation nanostructures and drug solubility, and importantly, decreases skin permeability. In this study, a gel-like lyotropic liquid crystal (LLC) was used as a tool to enhance skin permeability. In particular, we prepared 1-monolinolein (ML)-based LLCs with different water contents. All LLCs significantly enhanced skin permeation of a peptide drug, an epitope peptide of melanoma, despite their high viscoelasticity. Fourier transform infra-red spectroscopic analysis of the skin surface treated with the LLCs revealed that the gyroid geometry more strongly interacted with the lamellar structure inside the stratum corneum (SC) than the diamond geometry. Finally, as the result of the in vivo tumor challenge experiment using B16F10 melanoma-bearing mice, the LLC with the gyroid geometry showed stronger vaccine effect against tumor than a subcutaneous injection. Collectively, ML-based LLCs, especially with the gyroid geometry, are a promising strategy to deliver biomacromolecules into skin. Statement of significance: Transcutaneous drug delivery is a promising method for drug repositioning and reformulation because of its non-invasive and easy-to-use features. To overcome the skin barrier, which is the biggest challenge in transcutaneous drug delivery, we used a gel-like lyotropic liquid crystal (LLC) as a novel tool to enhance skin permeability. In this paper, we demonstrated that an LLC with a specific liquid crystalline structure has the highest skin permeation enhancement effect for a peptide antigen as a model drug. Moreover, the peptide antigen-loaded LLC showed a vaccine effect that was comparable to a subcutaneous injection in vivo. This study provides a basis for designing a transcutaneous delivery system of peptide drugs with LLC.

DOI： 10.1016/j.actbio.2021.11.008

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： https://doi.org/10.1016/j.molliq.2021.118103

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1021/acsami.1c11533

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1021/acs.molpharmaceut.1c00324

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1021/acsabm.1c00563

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Chemotherapeutic cytotoxic agents such as paclitaxel (PTX) are considered essential for the treatment of various cancers. However, PTX injection is associated with severe systemic side effects and high rates of patient noncompliance. Micelle formulations (MFs) are nano-drug delivery systems that offer a solution to these problems. Herein, we report an advantageous carrier for the transdermal delivery of PTX comprising a new MF that consists of two biocompatible surfactants: cholinium oleate ([Cho][Ole]), which is a surface-active ionic liquid (SAIL), and sorbitan monolaurate (Span-20). A solubility assessment confirmed that PTX was readily solubilized in the SAIL-based micelles via multipoint hydrogen bonding and cation-π and π-π interactions between PTX and SAIL[Cho][Ole]. Dynamic light scattering (DLS) and transmission electron microscopy revealed that in the presence of PTX, the MF formed spherical PTX-loaded micelles that were well-distributed in the range 8.7-25.3 nm. According to DLS, the sizes and size distributions of the micelle droplets did not change significantly over the entire storage period, attesting to their physical stability. In vitro transdermal assessments using a Franz diffusion cell revealed that the MF absorbed PTX 4 times more effectively than a Tween 80-based formulation and 6 times more effectively than an ethanol-based formulation. In vitro and in vivo skin irritation tests revealed that the new carrier had a negligible toxicity profile compared with a conventional ionic liquid-based carrier. Based on these findings, we believe that the SAIL[Cho][Ole]-based MF has potential as a biocompatible nanocarrier for the effective transdermal delivery of poorly soluble chemotherapeutics such as PTX.

DOI： 10.1021/acsami.1c03111

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Human skin contains numerous antigen-presenting cells that are a potential target for several immune-based therapies, including vaccination and cancer immunotherapy. However, the outermost layer of the skin-the stratum corneum-acts as a major physical barrier against the permeation of antigens that have a molecular weight > 500 Da. In this study, an ionic liquid-assisted delivery system (ILDS) was developed, which enabled the successful transdermal delivery of an antigenic protein, ovalbumin (OVA), with a toll-like receptor agonist, imiquimod, as an adjuvant, to stimulate a specific immune response. Both the ionic liquids and ILDS were completely biocompatible for topical or transdermal application for therapeutic purposes. The skin permeation of the antigenic protein and adjuvant was found to be significantly enhanced because of the incorporation of a surface-active ionic liquid in the ILDS. An in vivo immunization study showed that there was a high level of OVA-specific IgG antibody production because of the enhanced permeation of the antigen and adjuvant across and into the skin. In a preclusive anticancer study, vaccination through ILDS showed stronger tumor-growth inhibition compared to control group. These results indicated that the ILDS could be a promising strategy for transdermal immunization as future therapeutics.

DOI： 10.1016/j.ijpharm.2021.120582

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： https://doi.org/10.1016/j.ejps.2020.105667

記述言語：英語   掲載種別：研究論文（学術雑誌）  

The objective of this study was to prepare a co-amorphous formulation of piroxicam (PIR), a non-steroidal anti-inflammatory drug, and citric acid (CA), and evaluate its skin permeation ability. A spray-drying method was employed to prepare the co-amorphous formulation and its physical properties were characterized. X-ray powder diffraction and thermal analysis confirmed a homogeneous amorphous state, and the infrared spectra revealed intermolecular interactions between PIR and CA, suggesting formation of a co-amorphous formulation of PIR and CA. The PIR-CA co-amorphous formulation exhibited no crystallization for 60 days at 4/25/40°C with silica gel. The PIR-CA co-amorphous formulation increased the solubility of PIR in polyethylene glycol 400 compared with that of the pure drug, and physical mixture (PM) of PIR and CA, confirming a supersaturated state in the formulation. The PIR-CA co-amorphous formulation demonstrated higher skin permeation than PIR alone or PM of PIR and CA, and the flux value was consistent with the degree of saturation. Thus, the increase in the skin permeation of PIR from the PIR-CA co-amorphous formulation directly depended on the increased thermodynamic activity by supersaturation in the absence of interactions between the drug and co-former in the vehicle.

DOI： 10.1016/j.ejps.2020.105667

記述言語：英語   掲載種別：研究論文（学術雑誌）  

その他リンク： https://doi.org/10.1016/j.ejps.2020.105521

記述言語：英語   掲載種別：研究論文（学術雑誌）  

その他リンク： https://doi.org/10.1016/j.molliq.2020.114424

記述言語：英語   掲載種別：研究論文（学術雑誌）  

その他リンク： https://doi.org/10.1039/d0cc04491a

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1021/acs.molpharmaceut.0c00598

記述言語：英語   掲載種別：研究論文（学術雑誌）  

その他リンク： https://doi.org/10.1016/j.molliq.2020.113603

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.3390/COSMETICS7030052

記述言語：英語   掲載種別：研究論文（学術雑誌）  

その他リンク： https://doi.org/10.3390/pharmaceutics12090814

記述言語：英語   掲載種別：研究論文（学術雑誌）  

その他リンク： https://dx.doi.org/10.1021/acssuschemeng.0c03419

記述言語：英語   掲載種別：研究論文（学術雑誌）  

その他リンク： https://doi.org/10.1021/acssuschemeng.0c03205

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Transdermal delivery of drugs is more challenging for drugs that are insoluble or sparingly soluble in water and most organic solvents. To overcome this problem, ionic liquid (IL)-mediated ternary systems have been suggested as potential drug carriers. Here, we report potent ternary (IL–EtOH–IPM) systems consisting of biocompatible ILs, ethanol (EtOH), and isopropyl myristate (IPM) that can dissolve a significant amount of the sparingly soluble drug acyclovir (ACV). The ternary systems were optically transparent and thermodynamically stable with a wide range of IL pertinence. An in vitro drug permeation study showed that the ILs in the ternary systems dramatically enhanced ACV permeation into and across the skin. Fourier Transform Infrared spectroscopy of the stratum corneum (sc) after treatment with ternary systems showed that the skin barrier function was reduced by disturbance of the regularly ordered arrangement of corneocytes and modification of the surface properties of the sc during permeation. Histological analysis, and skin irritation studies using a reconstructed human epidermis model showed the safety profile of the ternary system, and there were no significant changes in the structures of the sc, epidermis, and dermis. Therefore, ternary systems containing biocompatible ILs are promising for transdermal delivery of insoluble or sparingly soluble drugs.

DOI： 10.1016/j.ijpharm.2020.119335

記述言語：英語   掲載種別：研究論文（学術雑誌）  

その他リンク： https://dx.doi.org/10.1021/acsomega.0c00867

記述言語：英語   掲載種別：研究論文（学術雑誌）  

The transdermal delivery of sparingly soluble drugs is challenging due to of the need for a drug carrier. In the past few decades, ionic liquid (IL)-in-oil microemulsions (IL/O MEs) have been developed as potential carriers. By focusing on biocompatibility, we report on an IL/O ME that is designed to enhance the solubility and transdermal delivery of the sparingly soluble drug, acyclovir. The prepared MEs were composed of a hydrophilic IL (choline formate, choline lactate, or choline propionate) as the non-aqueous polar phase and a surface-active IL (choline oleate) as the surfactant in combination with sorbitan laurate in a continuous oil phase. The selected ILs were all biologically active ions. Optimized pseudo ternary phase diagrams indicated the MEs formed thermodynamically stable, spherically shaped, and nano-sized (<100 nm) droplets. An in vitro drug permeation study, using pig skin, showed the significantly enhanced permeation of acyclovir using the ME. A Fourier transform infrared spectroscopy study showed a reduction of the skin barrier function with the ME. Finally, a skin irritation study showed a high cell survival rate (>90%) with the ME compared with Dulbecco’s phosphate-buffered saline, indicates the biocompatibility of the ME. Therefore, we conclude that IL/O ME may be a promising nano-carrier for the transdermal delivery of sparingly soluble drugs.

DOI： 10.3390/pharmaceutics12040392

記述言語：英語   掲載種別：研究論文（学術雑誌）  

生体適合性のイオン液体を合成し、経皮薬物キャリアとしてワクチンに有効であることを明らかにした。

その他リンク： https://doi.org/10.1021/acssuschemeng.9b07773

記述言語：英語   掲載種別：研究論文（学術雑誌）  

An allergy to cow’s milk proteins is the most common food allergy in infants and toddlers. Conventional oral immunotherapy for cow’s milk allergies requires hospital admission due to the risk of severe allergic reactions, including anaphylaxis. Therefore, a simpler and safer immunotherapeutic method is desirable. We examined transcutaneous immunotherapy with a solid-in-oil (S/O) system. In the S/O system, nano-sized particles of proteins are dispersed in an oil-vehicle with the assistance of nonionic surfactants. In the present study, the S/O system enhanced the skin permeation of the allergen molecule β-lactoglobulin (BLG), as compared with a control PBS solution. The patches containing BLG in the S/O nanodispersion skewed the immune response in the allergy model mice toward T helper type 1 immunity, indicating the amelioration of allergic symptoms. This effect was more pronounced when the immunomodulator resiquimod (R-848) was included in the S/O system.

DOI： 10.3390/pharmaceutics12030205

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Japanese cedar pollinosis (JCP) is a common affliction caused by an allergic reaction to cedar pollen and is considered a disease of national importance in Japan. Antigen-specific immunotherapy (AIT) is the only available curative treatment for JCP. However, low compliance and persistence have been reported among patients subcutaneously or sublingually administered AIT comprising a conventional antigen derived from a pollen extract. To address these issues, many research studies have focused on developing a safer, simpler, and more effective AIT for JCP. Here, we review the novel antigens that have been developed for JCP AIT, discuss their different administration routes, and present the effects of anti-allergy treatment. Then, we describe a new form of AIT called transcutaneous immunotherapy (TCIT) and its solid-in-oil (S/O) nanodispersion formulation, which is a promising antigen delivery system. Finally, we discuss the applications of S/O nanodispersions for JCP TCIT. In this context, we predict that TCIT delivery by using a S/O nanodispersion loaded with novel antigens may offer an easier, safer, and more effective treatment option for JCP patients.

DOI： 10.3390/pharmaceutics12030240

記述言語：英語   掲載種別：研究論文（学術雑誌）  

The development of non-toxic ionic liquid-based active pharmaceutical ingredients (IL-APIs) for effective topical drug delivery is still challenging. The properties of IL-APIs can be boosted up by selecting potential biocompatible cations. Here, we introduced N-methyl-2-pyrrolidone (NMP) as a potent biocompatible counter ion to prepare ionic liquefied drugs for topical drug delivery. The cytotoxicity of NMP cation was investigated using mammalian cell lines (HepG2, NIH3T3 and L929 cells) and compared with conventional IL-forming cations. The synthesized NMP cation has lower toxicity than that of conventional IL-forming cations. The NMP cation showed at least 3.6, 15.2 and 58.9 times lower toxicity than that of conventional imidazolium, ammonium and phosphonium cations, respectively. The synthesized NMP-based ionic liquid (NMP-IL) was characterized using ¹H & ¹³C NMR, FT-IR, DSC and TGA. NMP-IL showed better physico-thermal stability, enhanced skin penetration, and enriched drug accumulation 2.6 times higher than that of IL [Cho][Ibu] in the target tissue. These results suggested that NMP cation based API-IL can be an effective biocompatible formulation for topical drug delivery by accumulating active drugs in the skin.

DOI： 10.1016/j.molliq.2019.112166

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Skin dendritic cells (DCs) such as Langerhans cells and dermal dendritic cells have a pivotal role in inducing antigen-specific immunity; therefore, transcutaneous cancer vaccines are a promising strategy to prophylactically prevent the onset of a variety of diseases, including cancers. The largest obstacle to delivering antigen to these skin DC subsets is the barrier function of the stratum corneum. Although reverse micellar carriers are commonly used to enhance skin permeability to hydrophilic drugs, the transcutaneous delivery of antigen, proteins, or peptides has not been achieved to date because of the large molecular weight of drugs. To achieve effective antigen delivery to skin DCs, we developed a novel strategy using a surfactant as a skin permeation enhancer in a reverse micellar carrier. In this study, glyceryl monooleate (MO) was chosen as a skin permeation enhancer, and the MO-based reverse micellar carrier enabled the successful delivery of antigen to Langerhans cells and dermal dendritic cells. Moreover, transcutaneous vaccination with the MO-based reverse micellar carrier significantly inhibited tumor growth, indicating that it is a promising vaccine platform against tumors.

DOI： 10.1021/acs.molpharmaceut.9b01104

記述言語：英語   掲載種別：研究論文（学術雑誌）  

As a biocompatible and designer solvents, ionic liquids (ILs) are extensively used for enzymatic conversion of substrates, particularly those that are insoluble or sparingly soluble in water and common organic solvents. More than a decade ago, the first-generation ILs involved in enzymatic reactions generally comprised an imidazolium cation and non-coordinating anions, such as tetrafluoroborate and hexafluorophosphate. Recently, focus has shifted to more environmentally acceptable second- and third-generation ILs comprising enzyme compatible cations (e.g., cholinium salts) and anions, such as amines and amino acids. A wide range of such ILs have been derived from readily available renewable resources and used in biocatalytic reactions. Compared with first-generation ILs, the use of enzymes in second- and third-generation ILs provides better activity and stability, and they are also attractive from both an environmental and an economic viewpoint. In this review, we report the recent advances of enzymatic reactions in second- and third-generation ILs. The intention of this review is not to cover first-generation ILs, but rather to update and overview the potential approaches developed within the last ten years for enzymatic reactions in second- and third-generation ILs.

DOI： 10.1016/j.bej.2019.107426

記述言語：英語   掲載種別：研究論文（学術雑誌）  

We report on the separation and recovery of scandium(III) from sulfate solutions using solvent extraction and a membrane transport system utilizing newly synthesized amic acid extractants. Scandium(III) was quantitatively extracted with 50 mmol dm^-3 N-[N,N-di(2-ethylhexyl)aminocarbonylmethyl]glycine (D2EHAG) or N-[N,N-di(2-ethylhexyl)aminocarbonylmethyl]phenylalanine (D2EHAF) in n-dodecane at pH 2 and easily stripped using a 0.5 mol dm^-3 sulfuric acid solution. The extraction mechanisms of scandium(III) extraction with D2EHAG and D2EHAF were examined, and it was established that scandium(III) formed a 1:3 complex with both extractants (HR), that is, Sc(SO₄)₂ ^- _aq + 1.5(HR)_2org ⇄ Sc(SO₄)R(HR)_2org + H⁺ _aq + SO₄ ^2- _aq. The equilibrium constants of extraction were evaluated to be 4.87 and 9.99 (mol dm^-3)^0.5 for D2EHAG and D2EHAF, respectively. D2EHAG and D2EHAF preferentially extracted scandium(III) with a high selectivity compared to common transition metal ions under high acidic conditions (0 < pH ≤ 3). In addition, scandium(III) was quantitatively transported from a feed solution into a 0.5 mol dm^-3 sulfuric acid receiving solution through a polymer inclusion membrane (PIM) containing D2EHAF as a carrier. Scandium(III) was completely separated thermodynamically from nickel(II), aluminum(III), cobalt(II), manganese(II), chromium(III), calcium(II), and magnesium(II), and partially separated from iron(III) kinetically using a PIM containing D2EHAF as a carrier. The initial flux value for scandium(III) (J_0,Sc = 1.9 × 10^-7 mol m^-2 s^-1) was two times higher than that of iron(III) (J_0,Fe = 9.3 × 10^-8 mol m^-2 s^-1).

DOI： 10.1021/acsomega.9b02540

記述言語：英語   掲載種別：研究論文（学術雑誌）  

En masse vaccination is a promising strategy for combatting infectious diseases. Intranasal vaccination is a viable route of mass vaccination, and it could be performed easily via needle-free administration. However, it is not widely used because it tends not to evoke sufficient immunity. The aim of the present study was to improve the performance of intranasal vaccination by extending the amount of time that administered antigens remain in the nasal cavity, and enhancing immune responses via a nanocarrier-based adjuvant. A simple and safe solid-in-oil (S/O) system was investigated as a nanocarrier in intranasal vaccination. S/O nanodispersions are oil-based dispersions of antigens coated with surfactants. Because of the mucoadhesive capacities of surfactant and oil they have high potential to extend the amount of time that administered antigens remain in the nasal cavity, and can induce strong immune responses due to a nanocarrier-based adjuvant effect. In nasal absorption experiments antigens administered intranasally via S/O nanodispersions remained in the nasal cavity longer and induced strong mucosal and systemic immune responses. Histopathology analysis indicated that S/O nanodispersions did not modify the nasal epithelium or cilia, suggesting non-toxicity of the carrier. These results indicate the potential of intranasal vaccination using S/O nanodispersions for future vaccination.

DOI： 10.1016/j.ijpharm.2019.118777

記述言語：英語   掲載種別：研究論文（学術雑誌）  

In this stuy, we report the separation of P(II) an Rh(III) in a chlorie solution using a polymer inclusion membrane (PIM). We esigne a trioctyl(oecyl) phosphonium chlorie (P₈₈₈₁₂Cl) ionic liqui as a metal carrier for the PIM separation system. The effects of PIM composition an experimental conitions were systematically investigate. The concentrations of hyrochloric aci in the fee solution an thiourea in the receiving solution were foun to play a crucial role in the success of selective separation. Uner the optimize conitions, P(II) coul be effectively separate from Rh(III) with a 98% recovery yiel an 99% purity. We also compare the performance of our esigne carrier, P₈₈₈₁₂Cl, to that of commercially available ionic liqui trihexyl(tetraecyl) phosphonium chlorie (P₆₆₆₁₄Cl) using a 7-cycle reusability test. The P₈₈₈₁₂Cl showe a more stable performance an better urability compare with those of the commercial ionic liqui carrier.

DOI： 10.1021/acs.iecr.9b05183

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Japanese cedar pollinosis is a type I allergic disease and has already become a major public health problem in Japan. Conventional subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) cannot meet patients’ needs owing to the side effects caused by both the use of conventional whole antigen molecules in the pollen extract and the administration routes. To address these issues, a surface-modified antigen and transcutaneous administration route are introduced in this research. First, the pollen extract (PE) was conjugated to galactomannan (PE-GM) to mask immunoglobulin E (IgE)-binding epitopes in the PE to avoid side effects. Second, as a safer alternative to SCIT and SLIT, transcutaneous immunotherapy (TCIT) with a solid-in-oil (S/O) nanodispersion system carrying PE-GM was proposed. Hydrophilic PE-GM was efficiently delivered through mouse skin using S/O nanodispersions, reducing the antibody secretion and modifying the type 1 T helper (Th1)/ type 2 T helper (Th2) balance in the mouse model, thereby demonstrating the potential to alleviate Japanese cedar pollinosis.

DOI： 10.3390/pharmaceutics11110563

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Ionic liquid (IL)surfactants have attracted great interest as promising substitutes for conventional surfactants owing to their exceptional and favorable physico-chemical properties. However, most IL surfactants are not eco-friendly and form unstable micelles, even when using a high concentration of the surfactant. In this study, we prepared a series of halogen-free and biocompatible choline–fatty-acid-based ILs with different chain lengths and degrees of saturation, and we then investigated their micellar properties in aqueous solutions. Characterization of the synthesized surface-active ILs (SAILs)was performed by
H and C nuclear magnetic resonance spectroscopy, Fourier transform infrared spectroscopy, differential scanning calorimetry, and elemental analysis. The surface-active properties of the SAILs were investigated by tensiometry, conductometry, and dynamic light scattering measurements. The critical micelle concentration of the SAILs was found to be 2–4 times lower than those of conventional surfactants. The thermodynamic properties of micellization (ΔG 0m, ΔH 0m, and ΔS 0m)indicate that the micellization process of the SAILs is spontaneous, stable, and entropy-driven at room temperature. The cytotoxicity of the SAILs was evaluated using mammalian cell line NIH 3T3. Importantly, [Cho][Ole]shows lower toxicity than the analogous ILs with conventional surfactants. These results clearly suggest that these environmentally friendly SAILs can be used as a potential alternative to conventional ILs for various purposes, including biological applications.

DOI： 10.1016/j.jcis.2019.04.095

記述言語：英語   掲載種別：研究論文（学術雑誌）  

In order to prevent common hypersensitivity reactions to paclitaxel injections (Taxol), we previously reported an ionic liquid-mediated paclitaxel (IL-PTX)formulation with small particle size and narrow size distribution. The preliminary work showed high PTX solubility in the IL, and the formulation demonstrated similar antitumor activity to Taxol, while inducing a smaller hypersensitivity effect in in vitro cell experiments. In this study, the stability of the IL-PTX formulation was monitored by quantitative HPLC analysis, which showed that IL-PTX was more stable at 4 °C than at room temperature. The in vivo study showed that the IL-PTX formulation could be used in a therapeutic application as a biocompatible component of a drug delivery system. To assess the in-vivo biocompatibility, IL or IL-mediated formulations were administered intravenously by maintaining physiological buffered conditions (neutral pH and isotonic salt concentration). From in vivo pharmacokinetics data, the IL-PTX formulation was found to have a similar systemic circulation time and slower elimination rate compared to cremophor EL mediated paclitaxel (CrEL-PTX). Furthermore, in vivo antitumor and hypersensitivity experiments in C57BL/6 mice revealed that IL-PTX had similar antitumor activity to CrEL-PTX, but a significantly smaller hypersensitivity effect compared with CrEL-PTX. Therefore, the IL-mediated formulation has potential to be an effective and safe drug delivery system for PTX.

DOI： 10.1016/j.ijpharm.2019.05.020

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Formulations based on conventional surfactants and organic solvents have been used as potential dispersants for oil-spill remediation. However, their toxicity restricts their usage in marine environments. As a low-toxicity alternative, in this article we report an oil dispersant based on a binary mixture of an ionic liquid surfactant, choline laurate ([Cho][Lau]), and a biosurfactant, lactonic sophorolipid. We investigated the micellar properties, including the critical micelle concentration, micellar interaction parameter (β), and activity coefficients (f
₁
and f
₂
) for the mixed surfactant system. A non-ideal and synergistic interaction between [Cho][Lau] and lactonic sophorolipid was observed. A stable oil-in-water emulsion formed at an optimal ratio of 40:60 (w/w) of [Cho][Lau] and lactonic sophorolipid. At this ratio, a dispersion effectiveness of 83% was achieved with a dispersant-to-oil ratio of 1:25 (v/v). We observed the dispersed oil droplets with an optical microscope and evaluated their size using dynamic light scattering. The droplet size decreased with increasing dispersant-to-oil ratio. We also assessed the toxicity of the binary surfactant mixture in zebra fish (Danio rerio). Based on this assessment, the mixture can be classified as non-toxic. Therefore, the mixture of [Cho][Lau] and lactonic sophorolipid is a potential alternative to conventional toxic oil-spill dispersants.

DOI： 10.1016/j.molliq.2019.02.049

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Immune checkpoint inhibitors and adoptive transfer of gene-engineered T cells have emerged as novel therapeutic modalities for hard-to-treat solid tumors; however, many patients are refractory to these immunotherapies, and the mechanisms underlying tumor immune resistance have not been fully elucidated. By comparing the tumor microenvironment of checkpoint inhibition–sensitive and –resistant murine solid tumors, we observed that the resistant tumors had low immunogenicity. We identified antigen presentation by CD11b ⁺ F4/80 ⁺ tumor–associated macrophages (TAMs) as a key factor correlated with immune resistance. In the resistant tumors, TAMs remained inactive and did not exert antigen-presenting activity. Targeted delivery of a long peptide antigen to TAMs by using a nano-sized hydrogel (nanogel) in the presence of a TLR agonist activated TAMs, induced their antigen-presenting activity, and thereby transformed the resistant tumors into tumors sensitive to adaptive immune responses such as adoptive transfer of tumor-specific T cell receptor–engineered T cells. These results indicate that the status and function of TAMs have a significant impact on tumor immune sensitivity and that manipulation of TAM functions would be an effective approach for improving the efficacy of immunotherapies.

DOI： 10.1172/JCI97642

記述言語：英語   掲載種別：研究論文（学術雑誌）  

The technological utility of active pharmaceutical ingredients (APIs) is enormously improved when they are converted into ionic liquids (ILs). API-ILs possess better aqueous solubility and thermal stability than that of solid-state salt or crystalline drugs. However, many such API-ILs are not biocompatible or biodegradable. In the current study, we synthesized a series of IL-APIs using methotrexate (MTX), a potential anticancer prodrug, and biocompatible IL-forming cations (choline and amino acid esters). The MTX-IL moieties were characterized through
¹
H NMR, FTIR, p-XRD, DSC and thermogravimetric analysis. The solubility of the MTX-ILs was evaluated in simulated body fluids (phosphate-buffered saline, simulated gastric, and simulated intestinal fluids). An assessment of the in vitro antitumor activity of the MTX-ILs in a mammalian cell line (HeLa cells) was used to evaluate their cytotoxicity. The MTX-ILs showed aqueous solubility at least 5000 times higher than that of free MTX and two orders of magnitude higher compared with that of a sodium salt of MTX in both water and simulated body fluids. Importantly, a proline ethyl ester MTX prodrug showed similar solubility as the MTX sodium salt but it provided improved in vitro antitumor activity. These results clearly suggest that the newly synthesized API-ILs represent promising potential drug formulations.

DOI： 10.1016/j.molliq.2019.01.063

記述言語：英語   掲載種別：研究論文（学術雑誌）  

The recovery of platinum group metals (PGMs) from automotive exhaust catalysts is important, and hydrometallurgical extraction is an effective approach. In the present study, a newly designed phosphonium-based ionic liquid (IL) was applied to the separation and recovery of PGMs from an automobile catalyst leach liquor in conjunction with varying pH levels. This IL, trioctyldodecyl phosphonium chloride (P_8,8,8,12Cl), allows quantitative extraction of Pd(II) at any HCl concentration, with almost 80% removal of Rh(III) at 1 mol L^-1 HCl after two extractions. Significant amounts of Fe(III) were extracted into the IL phase, but could be removed using 1 mol L^-1 Na₂SO₃. The Pd(II) and Rh(III) were selectively recovered from the IL using 1 mol L^-1 CS(NH₂)₂ and 5 mol L^-1 HCl, respectively. This work therefore demonstrated the selective recovery of PGMs through optimization of various parameters and shows the significant potential of this IL with regard to recycling PGMs from leach liquor.

DOI： 10.1021/acs.iecr.8b05848

記述言語：英語   掲載種別：研究論文（学術雑誌）  

This paper reports on the development of a polymer inclusion membrane (PIM) for the selective separation of Sc(III) from other REM ions. A comparison is made of the performance of cellulose triacetate (CTA) based PIMs containing 2-thenoyltrifluoroacetone (HTTA), 2-ethylhexylphosphoric acid mono-2-ethylhexyl ester (PC-88A), N-[N,N-di(2-ethylhexyl) aminocarbonylmethyl]glycine (D2EHAG) or N-[N,N-di(2-ethylhexyl)aminocarbonylmethyl]phenylalanine (D2EHAF) as the carrier in the extraction of Sc(III) from its sulfuric acid/ammonium sulfate buffer solutions. The potential of the PIM containing D2EHAF for the selective separation of Sc(III) from a feed solution containing similar concentrations of Y(III), La(III), Nd(III), and Dy(III) into a 0.5 mol L⁻¹ sulfuric acid receiving solution has been demonstrated. In addition, the newly developed PIM containing D2EHAF exhibited excellent stability in 5 cycles of extraction and back-extraction of Sc(III) with insignificant deterioration in its performance. The results obtained in this study indicate that the molecular structure of the carrier has a strong influence on membrane stability, and that the introduction of a phenyl group into the carrier molecule results in a significant stability improvement.

DOI： 10.1016/j.memsci.2018.11.021

記述言語：英語   掲載種別：研究論文（学術雑誌）  

A supported liquid membrane (SLM) system for the selective separation of platinum(IV) from palladium(II) has been developed. The SLM was prepared using imidazolium-based IL 1-octy-3-methylimidazolium bis(trifluoromethanesulfonyl)- imide. The initial flux and separation factor of Pt(IV) from Pd(II) were found to significantly depend on the composition of the receiving solution. Based on the performance, a 0.1 mol dm
^-3
NaClO
₄
solution was selected as a suitable receiving solution. Membrane transport experiments showed that 93% of Pt(IV) can be selectively transported into the receiving solution, whereas most Pd(II) remains in the feed solution.

DOI： 10.2116/analsci.18N020

記述言語：英語   掲載種別：研究論文（学術雑誌）  

We herein designed bi-functional aromatic peptide amphiphiles both self-assembling to fibrous nanomaterials and working as a substrate of microbial transglutaminase, leading to peptidyl scaffolds with different morphologies that can be enzymatically post-functionalized with proteins.

DOI： 10.1039/C8CC08163H

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Extractant-impregnated resins (EIRs) prepared from 2-ethylhexyl phosphonic acid mono-2-ethylhexyl ester (commercial name PC-88A), neodecanoic acid (Versatic 10), and XAD-7HP polymeric beads have been developed for separation and pre-concentration of scandium (Sc). The separation factors between Sc and other metal ions are very high, allowing for selective recovery of Sc from a complex metal-mixture solution. Furthermore, desorption of Sc is quantitatively achieved using 2 M sulfuric acid, which is difficult for single-extractant-impregnated resins. The adsorption behavior, kinetics, and loading capacity of the binary EIR were investigated. The good reusability of the resin was confirmed by five times repeated use in recycling operation. This binary-extractant-impregnated concept could provide a new way to develop novel ion-exchange resins for metal separation.

DOI： 10.1252/jcej.18we175

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Cancer vaccines aim to prevent or inhibit tumor growth by inducing an immune response to tumor-associated antigens (TAAs) encoded by or present in the vaccine. Previous work has demonstrated that effective antitumor immunity can be induced using a codelivery system in which nonspecific immunostimulatory molecules are administered together with TAAs. In this study, we investigated the antitumor effects of a solid-in-oil (S/O) nanodispersion system containing a model TAA, ovalbumin (OVA), and resiquimod (R-848), a small molecular Toll-like receptor 7/8 ligand, which induces an antigen-nonspecific cellular immune response that is crucial for the efficacy of cancer vaccines. R-848 was contained in the outer oil phase of S/O nanodispersion. Analysis of OVA and R-848 permeation in mouse skin after application of an R-848 S/O nanodispersion indicated that R-848 rapidly permeated the skin and preactivated Langerhans cells, resulting in efficient uptake of OVA and migration of antigen-loaded Langerhans cells to the draining lymph nodes. Transcutaneous immunization of mice with an R-848 S/O nanodispersion inhibited the growth of E.G7-OVA tumors and prolonged mouse survival to a greater extent than did immunization with an S/O nanodispersion containing OVA alone. Consistent with this observation, antigen-specific secretion of the Th1 cytokine interferon-γand cytolytic activity were both high in splenocytes isolated from mice immunized with R-848 S/O. Our results thus demonstrate that codelivery of R-848 significantly amplified the antitumor immune response induced by antigen-containing S/O nanodispersions and further suggest that S/O nanodispersions may be effective formulations for codelivery of TAAs and R-848 in transcutaneous cancer vaccines.

DOI： 10.1021/acsbiomaterials.9b00260

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Liquid marble (LM), a self-standing micro-scale aqueous droplet, emerges as a micro-bioreactor in biological applications. Herein, the potential of LM as media for cell-free synthesis and simultaneous immobilization of recombinant proteins is explored. Initially, formation of hydrogel marble (HM) by using an enzymatic disulfide-based hydrogelation technique is confirmed by incorporating three components, horseradish peroxidase (HRP), a tetra-thiolated poly(ethylene glycol) derivative, and glycyl-L-tyrosine, in LM. The compatibility of the enzymatic hydrogelation with cell-free protein synthesis in LM is then validated. Although the hydrogelation reduces the level of protein synthesis in LM when compared with that in a test tube, the biosynthesis of enhanced green fluorescent protein (EGFP) is achieved. Interestingly, EGFP synthesized in LM is entrapped in the HM, and the introduction of a cysteine residue to EGFP by genetic engineering further increases the amount of protein immobilization in the hydrogel matrices. These results suggest that the cell-free synthesis and HRP-catalyzed hydrogelation can be conducted in parallel in LM, and the eventual entrapment of the key components in HM is possible. Facile recovery of macromolecular products immobilized in HM by degrading the hydrogel network under reducing conditions should lead to the design of an easy-to-handle system to screen protein functions.

DOI： 10.1002/biot.201800085

記述言語：英語   掲載種別：研究論文（学術雑誌）  

The organophosphorus extractant 2-ethylhexylphosphonic acid mono-2-ethylhexyl ester (PC88A) is widely used for solvent extraction of rare earth elements in an acidic leaching solution, but stripping of the loaded metals is difficult because of the high affinity between the metals and the extractant. Adding 100 times the concentration of neodecanoic acid (Versatic 10) to the extractant solution reduces the extraction ability for scandium (Sc) and enables quantitative stripping of the loaded Sc with a mild acidic solution, such as a 1 M mineral acid. The loading capacity is dependent on the PC88A concentration, so PC88A is the main species responsible for Sc extraction in the binary mixture. Nuclear magnetic resonance spectroscopy (NMR) of the organic phases suggests a potential interaction between the mixed extractants through the change in the hydrogen bonding. This causes an antagonistic effect and facilitates efficient Sc stripping from the extractant solution, so this method could be used for scandium recovery in industry.

DOI： 10.1080/07366299.2018.1532139

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Ionic liquid (IL) surfactants have attracted great attention as potential alternatives to conventional surfactants because of their unique tailor-made physicochemical properties. However, in most cases, the aggregations formed by single IL surfactants in aqueous media are unstable, even when using a large amount of surfactant. To address this limitation, here we investigated the aggregation behavior of binary IL surfactant micelles composed of the ILs choline oleate ([Cho][Ol]) and choline laurate ([Cho][Lau]) in aqueous media using tensiometry and dynamic light scattering measurements. Micellar and interfacial parameters including critical micelle concentration (cmc), micellar interaction parameters (β), activity coefficients (f₁ and f₂), surface excess concentration (Г_max), minimum surface area per molecule (A_min), and the size of surfactant aggregates were studied. In addition, various thermodynamic parameters such as the Gibbs free energy of micellization (∆G^o
_mic), standard Gibbs free energy of adsorption (∆G^o
_ad), molar free energy (G_min), and the excess Gibbs free energy of micellization (ΔG_ex) were also evaluated. A non-ideal synergistic interaction was observed for the mixed IL surfactant system, which formed larger micelles (105–120 nm) compared with those formed with a single IL (86–102 nm). The formed micelles were found to be thermodynamically stable with regards to all the mole ratio of ILs system. The antimicrobial activity of the single as well of the mixed IL system against Gram-positive and -negative bacteria displayed a low toxicity profile that fell in the range of “practically harmless” (100–1000 mg L⁻¹). The results suggested that the micellar system composed of mixed IL surfactants provides unique physical, chemical, and biological properties may offer novel opportunities for various applications such as oil dispersants.

DOI： 10.1016/j.molliq.2018.06.101

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Paclitaxel (PTX) injection (i.e., Taxol) has been used as an effective chemotherapeutic treatment for various cancers. However, the current Taxol formulation contains Cremophor EL, which causes hypersensitivity reactions during intravenous administration and precipitation by aqueous dilution. This communication reports the preliminary results on the ionic liquid (IL)-based PTX formulations developed to address the aforementioned issues. The formulations were composed of PTX/cholinium amino acid ILs/ethanol/Tween-80/water. A significant enhancement in the solubility of PTX was observed with considerable correlation with the density and viscosity of the ILs, and with the side chain of the amino acids used as anions in the ILs. Moreover, the formulations were stable for up to 3 months. The driving force for the stability of the formulation was hypothesized to be the involvement of different types of interactions between the IL and PTX. In vitro cytotoxicity and antitumor activity of the IL-based formulations were evaluated on HeLa cells. The IL vehicles without PTX were found to be less cytotoxic than Taxol, while both the IL-based PTX formulation and Taxol exhibited similar antitumor activity. Finally, in vitro hypersensitivity reactions were evaluated on THP-1 cells and found to be significantly lower with the IL-based formulation than Taxol. This study demonstrated that specially designed ILs could provide a potentially safer alternative to Cremophor EL as an effective PTX formulation for cancer treatment giving fewer hypersensitivity reactions.

DOI： 10.1021/acs.molpharmaceut.8b00305

記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Recycling of spent platinum group metals (PGMs) has attracted much attention in order to overcome the problems associated with the low natural abundance of these resources. To recycle such metals, efficient hydrometallurgical processes are required. To improve the efficiency of these processes, we have designed a new phosphonium-based ionic liquid as an extraction solvent. This paper reports on the potential use of the ionic liquid for extraction and separation of PGMs, namely Pt(IV), Pd(II), and Rh(III). RESULTS: An ionic liquid, trioctyl(dodecyl)phosphonium chloride, P₈₈₈₁₂Cl, which was newly synthesized, showed highly efficient extraction for Pt(IV), Pd(II), and Rh(III). P₈₈₈₁₂Cl features several advantages as an extraction solvent, such as high hydrophobicity and low viscosity compared with those features of a commercial analogue, trihexyl(tetradecyl)phosphonium chloride (P₆₆₆₁₄Cl). The favorable features of our novel ionic liquid were reflected by its high extraction efficiency and low release of phosphorus from the ionic liquid into the aqueous feed solution. Stripping operations were possible, and the high reusability of the ionic liquid was confirmed. CONCLUSION: The novel ionic liquid P₈₈₈₁₂Cl is potentially useful as an extraction solvent for PGMs. Results highlight the strengths of ionic liquids and the tuneability of their properties through design of their molecular structure.

DOI： 10.1002/jctb.5544

記述言語：英語   掲載種別：研究論文（学術雑誌）  

The technological utility of active pharmaceutical ingredients (APIs) is greatly enhanced when they are transformed into ionic liquids (ILs). API-ILs have better solubility, thermal stability, and the efficacy in topical delivery than solid or crystalline drugs. However, toxicological issue of API-ILs is the main challenge for their application in drug delivery. To address this issue, 11 amino acid esters (AAEs) were synthesized and investigated as biocompatible counter cations for the poorly water-soluble drug salicylic acid (Sal) to form Sal-ILs. The AAEs were characterized using ¹H and ¹³C NMR, FTIR, elemental, and thermogravimetric analyses. The cytotoxicities of the AAE cations, Sal-ILs, and free Sal were investigated using mammalian cell lines (L929 and HeLa). The toxicities of the AAE cations greatly increased with inclusion of long alkyl chains, sulfur, and aromatic rings in the side groups of the cations. Ethyl esters of alanine, aspartic acid, and proline were selected as a low cytotoxic AAE. The cytotoxicities of the Sal-ILs drastically increased compared with the AAEs on incorporation of Sal into the cations, and were comparable to that of free Sal. Interestingly, the water miscibilities of the Sal-ILs were higher than that of free Sal, and the Sal-ILs were miscible with water at any ratio. A skin permeation study showed that the Sal-ILs penetrated through skin faster than the Sal sodium salt. These results suggest that AAEs could be used in biomedical applications to eliminate the use of traditional toxic solvents for transdermal delivery of poorly water-soluble drugs.

DOI： 10.1016/j.ijpharm.2018.05.021

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Cancer vaccines represent a prophylactic or therapeutic method of suppressing cancer by activating the adaptive immune system. The immune response is initiated by the delivery of tumor antigens to antigen presenting cells (APCs). The use of peptides as vaccine antigens is advantageous, especially in the availability and productivity of pure and defined antigens. However, their limited immunogenicity remains a major drawback, and therefore, the utilization of nanocarriers as a means of delivering antigens to target cells and/or the addition of immune stimulants have been investigated as an efficient peptide-based cancer vaccine. We have developed a solid-in-oil (S/O) nanodispersion as a transcutaneous nanocarrier for hydrophilic molecules. This system has attractive features as a peptide nanocarrier for cancer vaccines, including transcutaneous targeting of professional APCs in the skin, high encapsulation efficacy of hydrophilic molecules, and capacity for coloading with a variety of immune stimulants such as adjuvants. We therefore sought to utilize the developed S/O nanodispersion for the delivery of the tyrosine-related protein 2 peptide, TRP-2_180-188, as a peptide antigen against melanoma. Transcutaneous vaccination of the S/O nanodispersion coloaded with adjuvant R-848 was associated with a significant inhibition of melanoma growth and suppression of lung metastasis in tumor-bearing mice. Our findings indicate the potential of S/O nanodispersions as an endogenous peptide carrier for cancer vaccines.

DOI： 10.1021/acs.molpharmaceut.7b00894

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Nanoparticles formed by the assembly of protein and polysaccharides are of great interest for the delivery of hydrophobic molecules. Herein, the formation of genipin-crosslinked nanoparticles from caseinate (CS) and chitosan (CH) is reported for the delivery of curcumin, a polyphenolic compound from turmeric, to cells. Genipin-crosslinked CS-CH nanoparticles (G-CCNPs) having a diameter of ∼250 nm and a low polydispersity index showed excellent stability over a wide pH range, as indicated by dynamic light scattering and transmission electron microscopic measurements. Cellular uptake of curcumin loaded into G-CCNPs by HeLa cells was improved, as measured by confocal laser scanning microscopy (CLSM) and fluorescence-activated cell-sorting analysis. Cell proliferation assays indicated that G-CCNPs were nontoxic and that curcumin's anticancer activity in vitro was also improved by G-CCNPs. Stability of curcumin at neutral pH was enhanced by G-CCNPs. CLSM study revealed that G-CCNPs were poorly internalized by HeLa cells, possibly because of strong cell membrane interactions and a negative zeta potential. Overall, our results suggested that the enhanced curcumin cytotoxicity might be associated with the enhanced stability of curcumin by G-CCNPs and free curcumin released from G-CCNPs into the cell. These biocompatible NPs might be suitable carriers for enhancing curcumin's therapeutic potential.

DOI： 10.1016/j.colsurfb.2018.01.041

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Phycocyanin (PC), a water-soluble protein-chromophore complex composed of hexameric (αβ)₆ subunits, has important biological functions in blue-green algae as well as pharmacological activities in biomedicine. We have previously developed a solid-in-oil (S/O) nanodispersion method to deliver biomacromolecules through the skin, although the transcutaneous mechanism has not yet been fully elucidated. To study the mechanism of transcutaneous protein delivery, we therefore enabled S/O nanodispersion by coating PC with hydrophobic surfactants and evaluated how the proteinaceous macromolecules formulated in an oil phase might permeate the skin. The extent of S/O nanodispersion of PC was dependent on the type of surfactant, suggesting that the selection of a suitable surfactant is crucial for encapsulating a large protein having a subunit structure. By measuring the intrinsic fluorescence of PC, we found that S/O nanodispersion facilitated the accumulation of PC in the stratum corneum (SC) of Yucatan micropig skin. Furthermore, after crossing the SC layer, the fluorescent recovery of PC was evident, indicating the release of the biologically active form of PC from the SC into the deeper skin layer.

DOI： 10.1016/j.ejpb.2018.01.020

記述言語：英語   掲載種別：研究論文（学術雑誌）  

This study reports on the selective separation of scandium (Sc) from other rare earth metals (REMs) using a polymer inclusion membrane (PIM). The PIM prepared with PC-88A (2-ethylhexyl hydrogen-2-ethylhexylphosphonate) alone as the carrier showed high extractability but the poor back-extraction of the extracted Sc³⁺ ions did not allow the transport of these ions to the receiving solution of a membrane transport system. To overcome this problem, a novel approach was introduced using a mixture of carriers that allowed Sc³⁺ transport into the receiving solution. A cellulose triacetate (CTA) based PIM containing both PC-88A and Versatic 10 (decanoic acid) as carriers and dioctyl phthalate (DOP) as a plasticizer was prepared for the selective separation of Sc³⁺ from other REM ions in nitrate media. The membrane composition was optimized and the effect of operational parameters such as pH of the feed solution and composition of the receiving solution was explored. The flux at the membrane/feed solution interface was found to depend significantly on the carrier concentration in the PIM, pH of the feed solution and the receiving solution acidity. The newly developed PIM allowed quantitative and selective transport of Sc³⁺ thus demonstrating its suitability for the selective recovery of this metal.

DOI： 10.1039/c7ra12697b

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Pharmaceutical application of ionic liquids (ILs), which are commonly defined as salt compounds composed of ionic species and melt below 100℃, is an attractive research field in a drug delivery system (DDS). The solubilization ability for insoluble drug molecules is a promising property of ILs. In 2010, it was reported that acyclovir, a sparingly soluble drug, was dissolved in imidazolium-based ILs, and the IL-in-oil microemulsions enhanced the transdermal delivery of acyclovir. The transdermal delivery is the most studied DDS field using ILs and some hydrophobic ILs were confirmed as skin penetration enhancers due to its higher interaction with the hydrophobic skin surface barrier. Utilization of active pharmaceutical ingredients (API) as the ions of ILs is known as an alternative strategy of IL-based DDSs because the API-IL enables to tune their physical or chemical properties of ILs. To improve the transdermal delivery, drugs were robed with hydrophobic counter ions. Recently, biocompatibility has been regarded as one of the most important properties of ILs for the DDS application. Several biomolecule-derived ions such as choline and amino acids were reported to form ILs and the biocompatible ILs were used as a solvent for solubilizing poorly soluble drugs and skin penetration enhancers. These researches suggest that ILs would be a promising solvent for developing a novel DDS.

DOI： 10.2745/dds.33.303

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Extraction behavior of rhodium (III) with a liquid surfactant membrane (LSM) containing an ionic liquid, 1-octyl-3-me-thylimidazolium hexafluorophosphate ([Omim][PF
₆
]), as a carrier from hydrochloric acid solutions has been investigated. At the optimum conditions, rhodium was selectively extracted over tin by using LSMs in which [Omim][PF
₆
] acted as the mobile carrier. The effects of important operational parameters on the recovery of rhodium were examined with three different stripping reagents for LSMs. It was found that the use of 2-amino-2- hydroxymethyl-1,3-propanediol (Tris) as a stripping reagent in LSMs was the key for the effective extraction of rhodium.

DOI： 10.1252/jcej.18we086

記述言語：英語   掲載種別：研究論文（学術雑誌）  

This paper reports on the selective separation and recovery of gold ions from leachates of discarded mobile phones using liquid-liquid extraction and a polymer inclusion membrane (PIM) transport system. The collected mobile phones were crushed by a mill and the obtained powder was calcinated. After leaching with aqua regia, the metal composition of the leachate was analyzed by inductively coupled plasma atomic emission spectrometry (ICP-AES). The analysis results confirmed that the mobile phone waste contained 397 g/ton of gold. Liquid-liquid extraction and PIM-based separation procedures for the selective recovery of gold(III) from synthetic and actual leachates were developed. The extracting organic solution and the PIM incorporated the newly synthesized extractant N-[N,N-di(2-ethylhexyl)aminocarbonylmethyl]glycine (D2EHAG) which exhibited high selectivity for the gold(III) ion over the other metal ions present in much higher concentrations in the leachates. The compositions of the feed and receiving solutions in both the liquid-liquid and PIM based extraction and back-extraction of the gold(III) ions were optimized. It was established that optimal extraction required a HCl concentration in the feed solution of 2 mol/L and that a receiving solution containing 0.1 M thiourea in 1 M HCl was capable of back-extracting gold(III) quantitatively. Membrane transport experiments with a synthetic leachate as the feed solution demonstrated that 96% of the gold(III) ions was selectively transported into the receiving solution of the transport cell thus leaving all other metal ions in the leachate.

DOI： 10.1016/j.seppur.2018.04.031

記述言語：英語   掲載種別：研究論文（学術雑誌）  

In the pharmaceutical industry, there are challenges in topical and transdermal administration of drugs, which are sparingly soluble in water and most organic solvents. Ionic liquids (ILs) have been found to be very effective for dissolution of sparingly soluble drugs. However, hydrophilic IL-borne drugs cannot penetrate into or across the skin because of the highly hydrophobic barrier function of the outer skin. In this chapter we report a novel IL-in-oil (IL/o) microemulsion (ME) that is able to dissolve a significant amount of sparingly soluble drug, acyclovir, in the IL core while the continuous oil phase can provide the desired features for topical/transdermal transport through the skin. The ME is composed of a blend of the nonionic surfactants polyoxyethylene sorbitan monooleate (Tween 80) and sorbitan laurate (Span 20), isopropyl myristate (IPM) as an oil phase, and the IL [C₁mim][(MeO)₂PO₂] (dimethylimidazolium dimethylphosphate) as a dispersed phase. The size and size distribution of the aggregates in the MEs were characterized by dynamic light scattering, showing formation of the nanocarrier in the size range 8-34 nm. In vitro drug permeation studies into and across the skin showed that the IL/o ME increased drug administration compared with other formulations. The safety profile of the new carrier was evaluated using a cytotoxicity assay on the human epidermal model LabCyte. We believe that these IL-assisted nonaqueous MEs can serve as a versatile and efficient nanodelivery system for sparingly soluble drug molecules.

DOI： 10.1039/9781788011839-00390

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DNA-protein conjugates are promising biomolecules for use in areas ranging from therapeutics to analysis because of the dual functionalities of DNA and protein. Conjugation requires site-specific and efficient covalent bond formation without impairing the activity of both biomolecules. Herein, we have focused on the use of a microbial transglutaminase (MTG) that catalyzes the cross-linking reaction between a glutamine residue and a primary amine. In a model bioconjugation, a highly MTG-reactive Gln (Q)-donor peptide (FYPLQMRG, FQ) was fused to enhanced green fluorescent protein (FQ-EGFP) and a primary amine-clustered DNA aptamer was enzymatically synthesized as a novel acyl-acceptor substrate of MTG, whose combination leads to efficient and convenient preparation of DNA-protein conjugates with high purity. Dual functionality of the obtained DNA-EGFP conjugate was evaluated by discrimination of cancer cells via c-Met receptor recognition ability of the DNA aptamer. The DNA aptamer-EGFP conjugate only showed fluorescence toward cells with c-Met overexpression, indicating the retention of the biochemical properties of the DNA and EGFP in the conjugated form.

DOI： 10.1021/acs.bioconjchem.7b00594

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Solid-in-oil (S/O) nanodispersion systems represent a new technology that has been developed in the last decade. Nano-sized, solid-state, hydrophilic drug molecules can be dispersed in an oil vehicle by coating the drug with hydrophobic surfactants; these materials are designated here as S/O nanodispersions. Conventional S/O nanodispersion systems were devised to maintain hydrophilic enzymes in their active form in organic solvents. Because the coated molecules are stable in non-aqueous media, S/O nanodispersion systems can be successfully applied in oral and skin drug deliveries. It is known that the permeability of hydrophilic drugs through the skin decreases when the molecular weight of the drug exceeds 500 Da. In addition, hydrophobic molecules tend to permeate through the skin preferentially, compared with hydrophilic molecules, because the outermost layer of the skin is hydrophobic. In our experiments, the permeation of hydrophilic biomolecules such as peptides and proteins through the skin increased by 4-7 times when their molecules were coated with lipophilic surfactants and dispersed in an oil vehicle. Here, we introduce an efficient method for drug delivery through the skin, using the S/O nanodispersion technique.

DOI： 10.1007/978-4-431-56526-0_18

記述言語：英語   掲載種別：研究論文（学術雑誌）  

The pharmaceutical industry faces a challenge to find potential solvents for drug molecules that are sparingly soluble in water and conventional organic solvents. Recently, ionic liquids (ILs) have attracted great attention as pharmaceutical solvents owing to their unique physicochemical and biological properties. In this study, the solubility of the sparingly soluble drug molecule acyclovir (ACV) in a wide variety of ILs was investigated by conductor-like screening model for real solvents (COSMO-RS) calculations. The predicted solubilities were validated by experimental measurements, and good agreement was found between the predicted and experimental results. The solubility of ACV was greatly affected by the structure of ILs, particularly the anionic moiety. Among the various ILs tested, ACV showed excellent solubility in ammonium-based ILs with an acetate anion. In vitro cytotoxicity of ILs to the MCF-10 normal breast epithelial cell line and cancer cell lines (MDA MB 231 and MCF 7) was investigated. The ammonium-based ILs showed higher IC₅₀ values than the imidazolium-based ILs with the acetate anion. Biodegradability results showed that diethylammonium acetate, triethylammonium acetate, and choline acetate ILs have high levels of biodegradation under aerobic conditions and can be classified as readily biodegradable. These findings will be useful for the design of IL-based drug delivery carriers that can act as versatile and efficient drug delivery systems for sparingly soluble drug molecules.

DOI： 10.1016/j.molliq.2017.08.020

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Pollinosis, a typical seasonal allergy, is a serious public health problem. Limited numbers of patients receive curative immunotherapy instead of symptomatic therapy; however, there are still some concerns about the inconvenience and side effects of subcutaneous injections and sublingual administration caused by immunotherapy. Here, we propose a simple and safe transcutaneous immunotherapy using solid-in-oil (S/O) nanodispersions loaded with vaccine T cell epitope peptides derived from pollen allergen. S/O nanodispersions are oil-based dispersions of antigens coated with hydrophobic surfactants. They have a high potential to deliver biomolecules including peptides or proteins to immune cells in the skin, and to induce an immune response. The result of quantitative and qualitative analysis by in vitro permeation experiments demonstrated the effective permeation of T cell epitope peptides into the skin. Furthermore, in vivo experiments using a pollinosis mouse model indicated that the S/O nanodispersions loaded with T cell epitopes suppressed serum antibody IgE and cytokine production, and alleviated allergic symptoms to a similar therapeutic level to that observed for subcutaneous injection. These results indicate the potential of transcutaneous immunotherapy using S/O nanodispersions for the future treatment of pollinosis.

DOI： 10.1016/j.ijpharm.2017.07.020

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

The recovery and separation of platinum group metals (PGMs) are of considerable significance for metal sustainability. To establish an efficient extraction process for PGMs, the novel extractant N-[N,N-di(2-ethylhexyl)aminocarbonylmethyl] phenylalanine (D2EHAF), containing a phenylalanine moiety as the metal-affinity group, was synthesized. The extraction of PGMs from aqueous HCl and HNO₃ solutions with D2EHAF, or our previously developed N-[N,N-di(2-ethylhexyl) aminocarbonylmethyl]glycine (D2EHAG), in n-dodecane was investigated. Both D2EHAF and D2EHAG exhibited high extraction affinities for Os⁴⁺, Pt⁴⁺, and Pd²⁺ in aqueous HCl. In a HNO₃ solution, D2EHAF extracted Pd²⁺ more efficiently than D2EHAG, and the extraction of Pd²⁺ from a 1 mol dm^-3 HNO₃ solution with D2EHAF proceeded quantitatively. The extracted metal ions were stripped from the organic solution using a highly acidic solution, or thiourea.

DOI： 10.1252/jcej.16we335

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Extraction and separation of Pt(IV) and Pd(II) from a hydrochloric acid solution was examined with a mixture of undiluted ionic liquids, 1-methyl-3-octylimidazolium bis(trifluoromethylsulfonyl)imide ([C8mim][Tf₂N]) and trihexyltetradecylphosphonium chloride ([P_6,6,6,14][Cl]). Imidazolium-based [C8mim][Tf₂N] shows a high selectivity for Pt(VI), whereas [P_6,6,6,14][Cl] has a high extraction ability for both Pt(IV) and Pd(II). The addition of [P_6,6,6,14][Cl] to [C8mim][Tf₂N] improved the extraction efficiency for Pt and the separation factor between Pt and Pd also increased. This improvement was attributed to the presence of Cl- being more hydrophilic than Tf₂N- in the [C8mim][Tf₂N] extraction phase. Stripping of the metals was possible with HNO3 solution without any degradation of the ionic liquid extraction phase. The ionic liquid mixture was shown to be reusable for at least five extraction cycles.

DOI： 10.15261/serdj.24.97

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1002/btm2.10048

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Transcutaneous vaccination is an attractive strategy that delivers antigen molecules topically into the skin to induce protective or therapeutic immune responses. In the last two decades, the skin has been regarded as a potential administration site for vaccines due to the abundant antigen presenting cells in the skin such as Langerhans cells and dermal dendritic cells, which are found in the epidermis or dermis. To create an efficient transcutaneous vaccine, the antigen needs to be penetrated across the stratum corneum, which is the outermost layer of the skin and possesses a high barrier function. To overcome this issue, various types of drug delivery systems have been proposed such as ultrasound, jet immunization and microneedles as physical methods, and penetration peptides, liposomes and nanoparticles as chemical methods. In this review, a solid-in-oil (S/O) nanodispersion, which is an oil-based drug carrier for proteins and peptides, and its application for transcutaneous protein delivery and vaccination are summarized. Along with comparing the S/O nanodispersion with the other oil-based drug carriers, the transdermal delivery of proteins such as insulin is introduced. Finally, basic immunological responses via transcutaneous administration with the S/O nanodispersion containing a model antigen, and researches on protect and therapeutic applications are summarized.

DOI： 10.2745/dds.32.176

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Sophorolipids (SLs) are surface active compounds that have excellent surface-lowering properties. Typically, SLs are produced using different hydrophobic substrates, such as alkanes, vegetable oils, and industrial effluents. The properties of the SLs are highly dependent on the hydrophobic substrate used for their production. The aim of the present study is to investigate the properties of SLs produced using three new hydrophobic substrates: Tapis oil, Melita oil, and Ratawi oil. The structures of the SLs were determined by Fourier transform infrared spectroscopy. The SLs yields using Tapis, Melita, and Ratawi oil were 26, 21, and 19 g L⁻¹, respectively. The SLs produced using Tapis, Melita, and Ratawi oil reduced the surface tension of pure water to 36.38, 37.84, and 38.92 mN/m, respectively, corresponding to critical micelle concentrations (CMCs) of 54.39, 55.68, and 58.34 mg L⁻¹. These values are comparable with SLs produced using palm oil (surface tension 35.38 mN/m and CMC 48.76 mg L⁻¹). The SLs produced using Tapis oil show a maximum emulsification activity of 71.2%. The produced SLs are active over the pH range 2–10 and for salinity up to 20% (w/v) NaCl. Thus, they show potential for various applications, including microbial enhanced oil recovery and oil spill remediation.

DOI： 10.1016/j.bej.2017.08.005

記述言語：英語   掲載種別：研究論文（学術雑誌）  

When a peptide amphiphile is dispersed in water, it self-assembles into a fibrous network, leading to a supramolecular hydrogel. When the gel is physically disrupted by shaking, it transforms into a sol state. After aging at room temperature for a while, it spontaneously returns to the gel state, called sol-gel transition. However, repeating the sol-gel transition often causes a change in the rheological properties of the gel. To gain a better understanding of the sol-gel transition and its reversibility, we herein examined the thermal motion of probe particles at different locations in a supramolecular hydrogel. The sol obtained by shaking the gel was heterogeneous in terms of the rheological properties and the extent decreased with increasing aging time. This time course of heterogeneity, or homogeneity, which corresponded to the sol-to-gel transition, was observed for the 1st cycle. However, this was not the case for the 2nd and 3rd cycles; the heterogeneity was preserved even after aging. Fourier-transform infrared spectroscopy, small-angle X-ray scattering, and atomic force and confocal laser scanning microscopies revealed that, although the molecular aggregation states of amphiphiles both in the gel and sol remained unchanged with the cycles, the fibril density diversified to high and low density regions even after aging. The tracking of particles with different sizes indicated that the partial mesh size in the high density region and the characteristic length scale of the density fluctuation were smaller than 50 nm and 6 μm, respectively.

DOI： 10.1039/c7sm01612c

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Protein-polymer conjugates have been developed in many fields. Most hybrids are composed of one protein attached to one or several polymer chains. The other form of hybrid involves the construction of multiple proteins on one polymer chain, thereby facilitating protein assemblies that provide multivalent effects. Unfortunately, synthetic methods for production of these types of hybrids are limited and challenging because precise control of the conjugation sites is needed. Herein, a novel synthetic polymer that can enzymatically assemble multiple proteins was developed. Polyacrylamide grafted with multiple microbial transglutaminase (MTG)-recognizable peptide derivatives was synthesized, and MTG-catalyzed site-specific conjugation of proteins with the polymer was achieved. The application for immunological biosensing was demonstrated using the assembly of a fusion protein composed of antibody-binding and enzyme moieties. This enzymatic method to synthesize a one-dimensional protein assembly on a synthetic polymer is versatile and can be expanded to a wide range of applications.

DOI： 10.1021/acs.biomac.6b01538

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Phenol is considered as pollutant due to its toxicity and carcinogenic effect. Thus, variety of innovative methods for separation and recovery of phenolic compounds is developed in order to remove the unwanted phenol from wastewater and obtain valuable phenolic compound. One of potential method is extraction using green based liquid organic solvent. Therefore, the feasibility of using palm oil was investigated. In this research, palm oil based organic phase was used as diluents to treat a simulated wastewater containing 300 × 10^-6of phenol solution using emulsion liquid membrane process (ELM). The stability of water-in-oil (W/O) emulsion on diluent composition and the parameters affecting the phenol removal efficiency and stability of the emulsion; such as emulsification speed, emulsification time, agitation speed, surfactant concentration, pH of external phase, contact time, stripping agent concentration and treat ratio were carried out. The results of ELM study showed that at ratio 7 to 3 of palm oil to kerosene, 5 min and 1300 r·min^− 1of emulsification process the stabile primary emulsion were formed. Also, no carrier is needed to facilitate the phenol extraction. In experimental conditions of 500 r·min^− 1of agitation speed, 3% Span 80, pH 8 of external phase, 5 min of contact time, 0.1 mol·L^− 1NaOH as stripping agent and 1:10 of treat ratio, the ELM process was very promising for removing the phenol from the wastewater. The extraction performance at about 83% of phenol was removed for simulated wastewater and an enrichment of phenol in recovery phase as phenolate compound was around 11 times.

DOI： 10.1016/j.cjche.2016.06.002

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1039/c6cc06985a

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1002/biot.201600081

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1002/jctb.4884

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.proeng.2016.06.464

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1039/c6md00358c

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.bej.2016.06.005

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1002/biot.201500603

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1252/jcej.15we293

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1002/jctb.4725

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.bej.2016.01.021

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1208/s12249-015-0333-x

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.biombioe.2015.05.023

記述言語：英語   掲載種別：研究論文（学術雑誌）  

特殊なナノコーティングによって、ガン抗原タンパク質をナノカプセル化し、担ガンマウスを用いて、ガンのワクチン効果を検証した。その結果、経皮投与によって、注射に匹敵するガンの抑制効果が観察された。

DOI： 10.1039/c5md00168d

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s11095-014-1554-5

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s11095-014-1554-5

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1039/c5md00378d

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1021/ja510156v

記述言語：英語  

DOI： 10.1252/jcej.14we162

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1252/jcej.14we240

記述言語：英語  

DOI： 10.1016/j.carbpol.2014.05.003

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1039/c4md00179f

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1252/jcej.14we052

記述言語：英語  

DOI： 10.1252/jcej.14we360

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1039/c4ra08897b

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.procbio.2014.02.016

記述言語：英語   掲載種別：研究論文（学術雑誌）  

The ionic liquid (IL), 1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ([Bmim][Tf₂N]), was evaluated as an extractant without dilution for the separation and recovery of precious metals. Au(III) was efficiently extracted from the aqueous phase to the IL phase, and a concentrated Au(III) solution almost 8 times higher than the initial feed solutions could be produced. In contrast, Pd(II) was rarely extracted and Pt(IV) was partly extracted under the present experimental conditions. Furthermore, the effect of the IL anions on the extraction ability for the metal ions was examined, and it was found that an IL having an anion component slightly more hydrophilic compared to [Tf₂N], such as 1-butyl-3-methylimidazolium hexafluorophosphate [Bmim][PF₆], showed a higher extraction ability than [Bmim][Tf₂N]. It was suggested that the extraction proceeded via an anion exchange mechanism and it was shown that ILs could be effective extractants for the separation of precious metals.

DOI： 10.15261/serdj.21.89

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Imidazolium-based ionic liquids (ILs) with Tf²N- as anions were studied as extractants without dilution for the extractive separation of platinum and palladium in an acidic chloride solution. The effect of the alkyl chain length on the extraction performance was evaluated and, based on the performance, the IL, 1-methyl-3-octylimidazolium bis(trifluoromethylsulfonyl) imide ([Omim][Tf²N]), was selected to be studied in detail. The extraction of Pt(IV) underwent little change over the HCl concentration studied, while that of Pd(II) decreased with increasing HCl concentration. The separation of Pt(IV) and Pd(II) was highly effective, and the highest separation factor between Pt(IV) and Pd(II) reached 312 at the optimum conditions in a binary component system composed of Pt(IV) and Pd(II). The effect of the initial Pt(IV) concentration on loading capacity and extraction efficiency of Pt(IV) was also investigated.

DOI： 10.15261/serdj.21.129

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1039/c4ra02901a

記述言語：英語  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1039/c3md00164d

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1021/ie403524a

記述言語：英語   掲載種別：研究論文（学術雑誌）  

注射を不要とするワクチン投与技術野開発に成功した。

DOI： 10.1016/j.ijpharm.2013.10.006

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語  

DOI： 10.1016/j.jhazmat.2013.03.026

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.biortech.2012.06.096

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1039/c2md20059g

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.ejpb.2012.05.016

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Enzyme-Mediated Protein Refolding

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Proteinase-mediated drastic morphological change of peptide-amphiphile to induce supramolecular hydrogelation

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Ionic liquid-assisted transdermal delivery of sparingly soluble drugs

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

A Comparative Study of SPG Membrane Emulsification in the Presence and Absence of Continuous-Phase Flow

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Preparation of Lactose-Modified Cellulose Films by a Nonaqueous Enzymatic Reaction and their Biofunctional Characteristics as a Scaffold for Cell Culture

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Simultaneous visual detection of single-nucleotide variations in tuna DNA using DNA/RNA chimeric probes and ribonuclease A

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Extraction Behavior of Indium with TOPO into Ionic Liquids

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Development of a novel immobilization method for enzymes from hyperthermophiles

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Design of a cytochrome P450BM3 reaction system linked by two-step cofactor regeneration catalyzed by a soluble transhydrogenase and glycerol dehydrogenase

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

"Spectrophotometric Assay for Protease Activity in Ionic Liquids Using Chromogenic Substrates".

記述言語：英語   掲載種別：研究論文（学術雑誌）  

CO2 separation facilitated by task-specific ionic liquids using a supported liquid membrane

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Formation of Reverse Micelles in a Room-Temperature Ionic Liquid

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1021/ac050782k

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1039/b505479f

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1021/la050364a

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1002/chem.200400691

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Hypoglycemic effect of surfactant-coated insulin solubilized in a novel solid-in-oil-in-water (S/O/W) emulsion

DOI： 10.1016/S0378-5173(02)00674-9

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Enantioselective transport of (S)-ibuprofen through a lipase-facilitated supported liquid membrane based on ionic liquids

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

Development of Microbioreactor for biodegradation of organic pollutants

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DNA hybridization in reverse micelles and its application to mutation detection

DOI： 10.1039/b208755n

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Novel surfactant for liquid surfactant membrane processes

DOI： 10.1252/jcej.20.157

出版者・発行元：Green Chemistry  

Deep eutectic solvents (DESs) composed of a beta-diketone and phosphine oxides featuring different alkyl chain lengths were prepared and then employed as liquid-liquid extraction and dissolution media for the separation of iron, cobalt, neodymium, and dysprosium. In the dissolution the more sterically hindered DESs exhibited enhanced selectivity to neodymium, which was poorly separated using liquid-liquid extraction. The dissolution selectivity in less sterically hindered DESs could be controlled by the addition of organic acids with different alkyl chain lengths.

DOI： 10.1039/d4gc01089b

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出版者・発行元：Journal of Molecular Liquids  

Quinine has traditionally been used in medicine to treat parasitic disease malaria due to its antimalarial activities. It is sparingly soluble in water and highly soluble in organic solvents. However, these solvents are not environmentally friendly, so greener solvents need to be explored and designed. Ionic liquids (ILs) were successfully observed to be greener and capable of dissolving biologically active compounds. However, finding a potential IL from millions of possible IL combinations is challenging. This work utilizes the conductor-like screening model for real solvents (COSMO-RS) to address this issue. This study aims to determine the dissolution behavior of quinine in ILs employing the COSMO-RS. A total of 540 IL combinations of 9 cations and 60 anions were investigated. The efficacy of each IL was evaluated by predicting the activity coefficients at infinite dilution, solvation-free energy, selectivity, capacity, and performance index (P.I.). This study reveals that ILs with shorter alkyl chains, polar and non-aromatic characteristics, and smaller anions are advantageous for the solubility enhancement of quinine. The most effective ILs, choline acetate, choline glycinate, and choline threoninate, displayed the highest selectivity, capacity, P.I., and lowest activity coefficient and solvation-free energies. The findings of the current study unlock key insights into the solubility behaviour of quinine in an aqueous solution employing ILs.

DOI： 10.1016/j.molliq.2024.125388

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出版者・発行元：Fisheries Science  

Ulva is an unutilized green seaweed that grows in the intertidal zone around the coast of Java Island, Indonesia. In this study, U. lactuca samples collected from three regions in south of Java Island (Cihara, Surade, and Tepus) were studied in terms of their chemical composition, physical properties and its bioactivity, to determine the best regions for establishing seaweed industries. The chemical characteristics differed significantly among different regions, where the seaweed from Tepus, Surade and Cihara had the highest content of protein (22.93%), carbohydrate (61.58%), and mineral (28.72%), respectively. The amino acids were dominated with L-aspartic acid and L-glutamic acid. All U. lactuca samples contained abundant pigments, such as chlorophylls and carotenoids, especially samples from Tepus. The highest content of crude ulvan was found in Surade seaweed (26.9%). Chemical and physical analyses showed the presence of S = O and C–O–S functional groups in ulvan, a sulfated polysaccharide unique to Ulva sp., with thermal degradation up to 220 °C. Crude ulvan from Surade and Tepus seaweed exhibited bioactivity to support proliferation of fibroblast cells at 100 and 1000 ppm, respectively. Based on the properties of U. lactuca, Tepus and Surade were identified as potential sites to establish aquaculture and/or processing industries.

DOI： 10.1007/s12562-024-01799-6

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記述言語：英語   出版者・発行元：Environmental Technology (United Kingdom)  

In the present investigation, a total of 108 combinations of ionic liquids (ILs) were screened using the conductor-like screening model for real solvents (COSMO-RS) with the aid of six cations and eighteen anions for the extraction of succinic acid (SA) from aqueous streams through dispersive liquid–liquid microextraction (DLLME). Using the screened ILs, an ionic liquid-based DLLME (IL-DLLME) was developed to extract SA and the role of different reaction parameters in the effectiveness of IL-DLLME approach was investigated. COSMO-RS results suggested that, quaternary ammonium and choline cations form effective IL combinations with [OH¯], [F¯], and [SO42¯] anions due to hydrogen bonding. In view of these results, one of the screened ILs, tetramethylammonium hydroxide [TMAm][OH] was chosen as the extractant in IL-DLLME process and acetonitrile was adopted as the dispersive solvent. The highest SA removal efficiency of 97.8% was achieved using 25 μL of IL [TMAm][OH] as a carrier and 500 μL of acetonitrile as dispersive solvent. The highest amount of SA was extracted with a stir time of 20 min at 300 rpm, followed by centrifugation for 5 min at 4500 rpm. Overall, the findings showed that IL-DLLME is efficient in extracting succinic acid from aqueous environments while adhering to the first-order kinetics.

DOI： 10.1080/09593330.2023.2234669

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出版者・発行元：Waste and Biomass Valorization  

Purpose: This work evaluated the profiles of Industrial agar seaweed waste biomass (ISWB) and pretreated ISWB by using deep eutectic solvent (DESs) and NaOH. The profiles of nanocellulose obtained from pretreated ISWB (with various types of hydrogen bond donors of choline chloride (ChCl)-based hydrated DES) were also evaluated. Methods: ISWB underwent pre-treatment with either 100% wt. DES (1:1 molar ratio of ethylene glycol: citric acid) or 10% wt. NaOH at 80 °C to 90 °C. Subsequent treatment involved 10% wt. DES or ChCl-based hydrated DES with various HBDs (oxalic acid, citric acid, and urea) in a 1:2 molar ratio to produce nanocellulose. Results: Cellulose nanofibers isolated by the CE-DES approach exhibited a substantially higher yield compared with those obtained via the CE-NaOH method. CE-DES method induced swelling of ISWB and facilitate production of cellulose nanofibers. SEM images of samples indicates the presence of fibrous nanostructures across the majority of the specimens. Fourier-transform infrared (FTIR) spectroscopy demonstrated uniformity among all samples; they exhibited a consistent fingerprint pattern. X-ray diffraction (XRD) spectra indicated the presence of cellulose Type I in cellulose nanofibers produced by CE–DES, but not definitively in nanocellulose produced by the CE–NaOH method. Conclusion: Cellulose nanofibers can be isolated from ISWB by using various DES and exhibits substantial characteristics of cellulose nanofibers from different ISWB pretreatment protocols. Graphical Abstract: (Figure presented.)

DOI： 10.1007/s12649-024-02499-z

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記述言語：英語   出版者・発行元：Molecules  

Herein, we report a transdermal patch prepared using an ionic liquid-based solid in oil (IL-S/O) nanodispersion and a pressure-sensitive adhesive (PSA) to deliver the macromolecular antigenic protein, ovalbumin (OVA). The IL-S/O nanodispersion and a PSA were first mixed at an equal weight ratio, then coated onto a release liner, and covered with a support film. To evaluate the effect of the PSA, three types of PSAs, DURO-TAK 87-4098, DURO-TAK 87-4287, and DURO-TAK 87-235A, were used to obtain the corresponding IL-S/O patches SP-4098, SP-4287, and SP-235A, respectively. The prepared IL-S/O patches were characterized for surface morphology, viscoelasticity, and moisture content. In vitro skin penetration and in vivo immunization studies of the IL-S/O patches were performed using Yucatan micropig skin and the C57BL/6NJc1 mice model, respectively. The SP-4098 and SP-4287 delivered 5.49-fold and 5.47-fold higher amounts of drug compared with the aqueous formulation. Although both patches delivered a similar amount of drug, SP-4287 was not detached fully from the release liner after 30 days, indicating low stability. Mice immunized with the OVA-containing SP-4098 produced a 10-fold increase in anti-OVA IgG compared with those treated with an aqueous formulation. These findings suggested that the IL-S/O patch may be a good platform for the transdermal delivery of antigen molecules.

DOI： 10.3390/molecules29132995

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Journal of Bioscience and Bioengineering  

Antibody drugs play a vital role in diagnostics and therapy. However, producing antibodies from mammalian cells is challenging owing to cellular heterogeneity, which can be addressed by applying droplet-based microfluidic platforms for high-throughput screening (HTS). Here, we designed an integrated system based on disulfide-bonded redox-responsive hydrogel beads (redox-HBs), which were prepared through enzymatic hydrogelation, to compartmentalize, screen, select, retrieve, and recover selected Chinese hamster ovary (CHO) cells secreting high levels of antibodies. Moreover, redox-HBs were functionalized with protein G as an antibody-binding module to capture antibodies secreted from encapsulated cells. As proof-of-concept, cells co-producing immunoglobulin G (IgG) as the antibody and green fluorescent protein (GFP) as the reporter molecule, denoted as CHO(IgG/GFP), were encapsulated into functionalized redox-HBs. Additionally, antibody-secreting cells were labeled with protein L-conjugated horseradish peroxidase using a tyramide amplification system, enabling fluorescence staining of the antibody captured inside the beads. Redox-HBs were then applied to fluorescence-activated droplet sorting, and selected redox-HBs were degraded by reducing the disulfide bonds to recover the target cells. The results indicated the potential of the developed HTS platform for selecting a single cell viable for biopharmaceutical production.

DOI： 10.1016/j.jbiosc.2024.04.001

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記述言語：英語   出版者・発行元：(公社)日本生物工学会  

掲載種別：研究論文（学術雑誌）  

DOI： 10.1021/acssusresmgt.4c00100

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出版者・発行元：ASEAN Journal of Chemical Engineering  

Ulva lactuca is a green seaweed commonly called sea lettuce and contains sulphated polysaccharides that have biological activity. Despite its lack of ecological sustainability, strong acids (HCl) and strong bases (NaOH) are widely used as solvents in the conventional extraction process for ulvan. Deep eutectic solvent (DES) is an alternative to ulvan extraction solvent, which is more environmentally friendly and has low toxicity. This study aims to assess the efficacy of peracetic acid (PAA) pretreatment and post-treatment in enhancing the quality of extracted ulvan using a DES-based solvent in the extraction process. Ulvan extraction using DES with a temperature of 85-95°C for 1 hour and adding 2% PAA pretreatment, 0.1%, 0.5%, and 2% PAA post-treatment were conducted. PAA pre-and post-treatment was carried out with a 1:10 (w/v) ratio at room temperature for 30 minutes. The analysis included moisture content, yield, functional groups, sulphate content, and color. The test results revealed that ulvan treated with 2% PAA pretreatment had the highest moisture content and sulphate content, at 18.71% and 33.39%, respectively, while ulvan treated with 0.1% PAA post-treatment had the highest yield, at 41.96%. Adding peracetic acid concentration can increase the color quality of the ulvan. PAA pre-and post-treatment had a significant effect on all ulvan quality parameters.

DOI： 10.22146/ajche.12272

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掲載種別：研究論文（学術雑誌）   出版者・発行元：ACS Sustainable Chemistry and Engineering  

The utilization of ionic liquids (ILs) in metal extraction has been massively studied due to their excellent extraction ability, vast structural tunability, and low volatility. However, several ILs can be severely toxic, depending on the structure. It is significant to extract metal ions in a greener way for sustainability, yet the development of low-toxicity ILs for metal extraction remains a challenge. We prepared a series of potentially biocompatible ILs composed of amino acid ester (AAE)-based cations, with varying alkyl chain lengths and amino acid types and a fixed linoleate anion. An in vitro cytotoxicity study on HeLa cells indicates that the EC50 value of the synthesized ILs was ca. 2 orders of magnitude higher than that of commercial ILs (Aliquat 336 and Cyphos 104), suggestive of the low toxicity of the newly synthesized ILs. The ILs extracted the transition metals in the following order: Ni2+ > Co2+ > Mn2+. The separation factors for Ni/Co and Co/Mn ranged from 0.8 to 55 and from 0.6 to 50, respectively. In addition, l-leucine butyl linoleate exhibited highly selective extraction toward Au3+ and Pd2+ over Pt4+ with separation factors for Au/Pt and Pd/Pt of 37 and 40 in 0.05 mol/L HCl, respectively. Thus, AAE-based ILs are promising biocompatible extractants for metals.

DOI： 10.1021/acssuschemeng.4c01799

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Chemical Communications  

Herein, we report ethosome (ET) formulations composed of a safe amount of 1,2-dimyristoyl-sn-glycero-3-phosphatidylcholine (DMPC)-based ionic liquid with various concentrations of ethanol as a carrier for the transdermal delivery of a high molecular weight drug, insulin. The Insulin-loaded ET vesicles exhibited long-term stability compared to conventional DMPC ETs, showing significantly higher drug encapsulation efficiency and increased skin permeation ability.

DOI： 10.1039/d3cc06130b

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：International Journal of Molecular Sciences  

Candida albicans is a prevalent fungal pathogen that displays antibiotic resistance. The polyene antifungal amphotericin B (AmB) has been the gold standard because of its broad antifungal spectra, and its liposomal formulation, AmBisome, has been used widely and clinically in treating fungal infections. Herein, we explored enhancing the antifungal activity of AmBisome by integrating a small chitin-binding domain (LysM) of chitinase A derived from Pteris ryukyuensis. LysM conjugated with a lipid (LysM–lipid) was initially prepared through microbial transglutaminase (MTG)-mediated peptide tag-specific conjugation of LysM with a lipid–peptide substrate. The AmBisome formulation modified with LysM–lipid conjugates had a size distribution that was comparable to the native liposomes but an increased zeta potential, indicating that LysM–lipid conjugates were anchored to AmBisome. LysM–lipid-modified AmBisome exhibited long-term stability at 4 °C while retaining the capacity to bind chitin. Nevertheless, the antifungal efficacy of LysM–lipid-modified AmBisome against C. albicans was modest. We then redesigned a new LysM–lipid conjugate by introducing a peptide linker containing a thrombin digestion (TD) site at the C-terminus of LysM (LysM–TD linker–lipid), thereby facilitating the liberation of the LysM domain from AmBisome upon the addition of thrombin. This new AmBisome formulation anchored with LysM–TD linker–lipid exhibited superior performance in suppressing C. albicans growth in the presence of thrombin compared with the LysM–lipid formulation. These results provide a platform to design stimuli-responsive AmBisome formulations that respond to external environments and thus advance the treatment of pathogenic fungi infections.

DOI： 10.3390/ijms25073567

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記述言語：その他   掲載種別：研究論文（学術雑誌）  

DOI： 10.1101/2024.03.04.583322

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記述言語：英語   出版者・発行元：Communications Chemistry  

Assessing the formation of a deep eutectic solvent (DES) necessitates a solid-liquid equilibrium phase diagram. Yet, many studies focusing on DES applications do not include this diagram because of challenges in measurement, leading to misidentified eutectic points. The present study provides a practical approach for estimating the phase diagram of any binary mixture from the structural information, utilizing machine learning and quantum chemical techniques. The selected machine learning model provides reasonably high accuracy in predicting melting point (R2 = 0.84; RMSE = 40.53 K) and fusion enthalpy (R2 = 0.84; RMSE = 4.96 kJ mol−1) of pure compounds upon evaluation by test data. By pinpointing the eutectic point coordinates within an extensive chemical space, we highlighted the impact of the mole fractions and melting properties on the eutectic temperatures. Molecular dynamics simulations of selected mixtures at the eutectic points emphasized the pivotal role of hydrogen bonds in dictating mixture behavior.

DOI： 10.1038/s42004-024-01116-3

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記述言語：その他   掲載種別：研究論文（学術雑誌）   出版者・発行元：Bioconjugate Chemistry  

Microbial transglutaminase (MTG) from Streptomyces mobaraensis is a powerful biocatalytic glue for site-specific cross-linking of a range of biomolecules and synthetic molecules that have an MTG-reactive moiety. The preparation of active recombinant MTG requires post-translational proteolytic digestion of a propeptide that functions as an intramolecular chaperone to assist the correct folding of the MTG zymogen (MTGz) in the biosynthesis. Herein, we report engineered active zymogen of MTG (EzMTG) that is expressed in soluble form in the host Escherichia coli cytosol and exhibits cross-linking activity without limited proteolysis of the propeptide. We found that the saturation mutagenesis of residues K10 or Y12 in the propeptide domain generated several active MTGz mutants. In particular, the K10D/Y12G mutant exhibited catalytic activity comparable to that of mature MTG. However, the expression level was low, possibly because of decreased chaperone activity and/or the promiscuous substrate specificity of MTG, which is potentially harmful to the host cells. The K10R/Y12A mutant exhibited specific substrate-dependent reactivity toward peptidyl substrates. Quantitative analysis of the binding affinity of the mutated propeptides to the active site of MTG suggested an inverse relationship between the binding affinity and the catalytic activity of EzMTG. Our proof-of-concept study provides insights into the design of a new biocatalyst using the MTGz as a scaffold and a potential route to high-throughput screening of EzMTG mutants for bioconjugation applications.

DOI： 10.1021/acs.bioconjchem.3c00544

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記述言語：その他   掲載種別：研究論文（学術雑誌）   出版者・発行元：ACS Biomaterials Science and Engineering  

Droplet-based high-throughput screening systems are an emerging technology that provides a quick test to screen millions of cells with distinctive characteristics. Biopharmaceuticals, specifically therapeutic proteins, are produced by culturing cells that secrete heterologous recombinant proteins with different populations and expression levels; therefore, a technology to discriminate cells that produce more target proteins is needed. Here, we present a droplet-based microfluidic strategy for encapsulating, screening, and selecting target cells with redox-responsive hydrogel beads (HBs). As a proof-of-concept study, we demonstrate the enrichment of hybridoma cells with enhanced capability of antibody secretion using horseradish peroxidase (HRP)-catalyzed hydrogelation of tetra-thiolate poly(ethylene glycol); hybridoma cells were encapsulated in disulfide-bonded HBs. Recombinant protein G or protein M with a C-terminal cysteine residue was installed in the HBs via disulfide bonding to capture antibodies secreted from the cells. HBs were fluorescently stained by adding the protein L-HRP conjugate using a tyramide signal amplification system. HBs were then separated by fluorescence-activated droplet sorting and degraded by reducing the disulfide bonds to recover the target cells. Finally, we succeeded in the selection of hybridoma cells with enhanced antibody secretion, indicating the potential of this system in the therapeutic protein production.

DOI： 10.1021/acsbiomaterials.3c01386

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記述言語：英語   出版者・発行元：日本溶媒抽出学会  

<p>We synthesized low-toxicity L-leucine propyl ester linoleate and L-leucine propyl ester oleate pseudo-protic ionic liquids (ILs) for benign extraction of Ni(II), Co(II), and Mn(II). The extraction ability order for both ILs was Ni(II) > Co(II) > Mn(II). In addition, we developed a machine learning model with an eXtreme Gradient Boosting regressor algorithm to evaluate and predict the ecotoxicity level of the ILs. An evaluation of the proposed regression model by cross-validation indicates that the model is reliable, with an R² value of 0.71. The prediction results indicate that the newly synthesized ILs are much less toxic than a commercially available IL (methyltrioctylammonium chloride) that is often used for metal extraction. </p>

DOI： 10.15261/serdj.31.31

CiNii Research

出版者・発行元：Journal of Chemical Engineering of Japan  

This study explored the potential for an environmentally friendly method for refining difficult-to-solubilise noble metals (notably platinum). Conventional noble-metal refining processes rely on the use of strong inorganic acids and oxidants, which cause significant environmental impact. To overcome these challenges, we propose a non-aqueous direct leaching process using an ionic liquid, an organic acid, and a chlorinating agent. Our findings indicate that trihexyl(tetradecyl)phosphonium chloride (P66614Cl) in combination with methanesulfonic acid and trichloroisocyanuric acid effectively solubilises metallic platinum. We investigated the leaching mechanism using ultraviolet–visible spectroscopy and confirmed that Pt(0) was oxidised to Pt(IV) to form PtCl62-Recovery of Pt from Pt-loaded P66614Cl was achieved by stripping with ammonium nitrate solution. . This work advances the development of sustainable refining methods for noble metals.

DOI： 10.1080/00219592.2023.2228363

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記述言語：英語   出版者・発行元：Chemosphere  

Chemical dispersants are extensively used for marine oil spill remediation. However, the increased toxicity and low biodegradability of these dispersants restrict their employment in the marine environment. Hence, in this work, we have developed an eco-friendly formulation composed of an ionic liquid,1-butyl-3-methylimidazolium lauroyl sarcosinate [BMIM][Lausar] and sorbitan monooleate (Span) 80. Micellar and interfacial parameters, dispersion effectiveness, as well as the toxicity and biodegradability of the developed formulation were investigated. Micellar properties confirmed a high degree of synergism among the surfactant molecules and the formation of stable micelle. The dispersion effectiveness, at dispersant-to-oil ratio (DOR) of 1:25 (v/v), against three crude oils (Arab, Ratawi, and Doba) was assessed. We achieved a dispersion effectiveness of 68.49%, 74.05%, and 83.43% for Ratawi, Doba, and Arab crude oil, respectively, using a 70:30 (w/w) ratio of Span 80 to [BMIM][Lausar]. Furthermore, the results obtained from optical microscopy and particle size analysis (PSA) indicated that the oil droplet size decreased with higher DOR. Additionally, acute toxicity experiments were conducted on zebrafish (Danio rerio) using the developed formulation, confirming its non-toxic behavior, with LC50 values of 800 mg/L after 96 h. The formulation also exhibited high biodegradability, with only 25.01% of the original quantity remaining after 28 days. Hence, these results suggest that the new formulation has the potential to be a highly effective and environmentally friendly dispersant for oil spill remediation.

DOI： 10.1016/j.chemosphere.2023.140412

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出版者・発行元：Arabian Journal for Science and Engineering  

In this age of cutting-edge technology, electronic equipment consumption, such as mobile phones, has increased tremendously. This was followed by a staggering increase in electronic waste (e-waste). However, it has been known that e-wastes contain higher amounts of precious metals than pristine sources, such as Au, which is valuable as an alternative precious metal source. Due to its various advantages, adsorption has emerged as one of the most common metal removal or recovery methods. A crucial aspect of adsorption is developing a cost-effective adsorbent for selective recovery of Au from the e-wastes. Thus, functionalized biomass-based adsorbent was developed to recover precious metals from e-waste. Functionalized activated carbon (ACIL900) has an appealing high adsorption capacity (116.2 mg g−1) performance and follows the chemisorption route, which fits with the monolayer model. The presence of IL boosts the adsorption efficiency due to its compatible interaction with the metal complexes. Remarkably, ACIL900 could quantitatively adsorb precious metals and several base metals from mobile phone leachate. The selective recovery of Au from the adsorbent was performed by sequential desorption using various solutions. Finally, Au was successfully recovered from the desorption solution using an electrochemical reduction process. ACIL900 was also found to maintain its performance for three adsorption–desorption cycles. This work reported the full recovery of Au from e-waste to its final pure product through the combination of adsorption, sequential desorption, and electrochemical reduction.

DOI： 10.1007/s13369-023-08327-1

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出版者・発行元：Arabian Journal for Science and Engineering  

The article "Functionalization of Biomass-derived Activated Carbon and Electrochemical Reduction for the Recovery of Gold from Mobile Phone Leachate", written by Mochamad Lutfi Firmansyah, Ilma Amalina, Intan Nurul Rizki, Asmaul Mashad Alfaza,Prastika Krisma Jiwanti, Aishah Abdul Jalil, Masahiro Goto, was originally published electronically on the publisher’s internet portal on 20 October 2023 without open access. With the author(s)’ decision to opt for Open Choice, the copyright of the article changed on 9th October 2023 to © The Author(s) 2023 and the article is forthwith distributed under a Creative Commons Attribution 4.0 Interna?tional License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit.

DOI： 10.1007/s13369-023-08499-w

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記述言語：英語   出版者・発行元：(公社)日本生物工学会  

ペルオキシダーゼ触媒によるクロスリンク形成を介して生理的な条件下でゲル化を受けるアルブミン派生物を合成した。アルブミンをカルボジイミドを用いてフェノール性水酸基(Alb-Ph-OH)で修飾し、置換度がゲル化に及ぼす影響を解析した。Alb-Ph-OHヒドロゲルの多様な特性、すなわち、ゲル化時間、膨張率、孔径、貯蔵弾性率、および酵素的な分解性は置換度とポリマー濃度の調整により容易に調節可能であった。Alb-Ph-OHヒドロゲル中にカプセル化された細胞の生存率は高かった。

記述言語：その他   掲載種別：研究論文（学術雑誌）   出版者・発行元：Journal of Bioscience and Bioengineering  

Albumin is an attractive component for the development of biomaterials applied as biomedical implants, including drug carriers and tissue engineering scaffolds, because of its high biocompatibility and low immunogenicity. Additionally, albumin-based gelators facilitate cross-linking reactions under mild conditions, which maintains the high viability of encapsulated living cells. In this study, we synthesized albumin derivatives to undergo gelation under physiological conditions via the peroxidase-catalyzed formation of cross-links. Albumin was modified with phenolic hydroxyl groups (Alb–Ph–OH) using carbodiimide chemistry, and the effect of degree of substitution on gelation was investigated. Various properties of the Alb–Ph–OH hydrogels, namely the gelation time, swelling ratio, pore size, storage modulus, and enzymatic degradability, were easily controlled by adjusting the degree of substitution and the polymer concentration. Moreover, the viability of cells encapsulated within the Alb–Ph–OH hydrogel was high. These results demonstrate the potential applicability of Alb–Ph–OH hydrogels as cell-encapsulating materials for biomedical applications, including tissue engineering.

DOI： 10.1016/j.jbiosc.2023.09.007

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記述言語：その他  

DOI： 10.1101/2023.10.09.561484

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記述言語：その他  

DOI： 10.1002/tcr.202380802

記述言語：日本語   出版者・発行元：日本DDS学会  

イオン液体の製剤利用に近年注目が集まっている。なかでも、イオン液体の経皮吸収促進機能は、小分子の薬物のみならず、ペプチドやタンパク質などのバイオ医薬品までおよび、非侵襲性の経皮製剤の開発に大変有用である。特に、イオン液体の製剤利用においては、イオン液体の安全性を担保することが重要な課題となっている。そこで本稿では、コリン、アミノ酸、脂肪酸そして脂質など、安全性の高い素材によって形成されたイオン液体を紹介する。生体適合性の高いイオン液体の活用によって、DDSの徐放特性を発揮する中分子医薬あるいは経皮ワクチンの開発が可能となった。最近では、核酸医薬などの新しいモダリティにも、イオン液体の利用に大きな期待が寄せられている。

DOI： 10.2745/dds.38.220

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Chemical Communications  

This study investigated the localization of artificial peptide supramolecular fibers in liquid?liquid phase separation (LLPS). Hierarchical organization led to the localization of supramolecules in LLPS droplets. Moreover, proteins were recruited into confined droplets by the physical adsorption of proteins on the supramolecules, enabling an enhanced cascade reaction.

DOI： 10.1039/D2CC05910J

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記述言語：日本語   出版者・発行元：日本膜学会  

Transdermal drug delivery is receiving a growing concern to alternate conventional drug administration techniques such as oral administration or needle–stick based administration methods. In this review article, we proposed a patch system based on a solid–in–oil nanodispersion technique as a simple and efficient delivery method of drugs, especially protein and peptide vaccines, through the skin. The skin is an attractive route for vaccination because there are many immune cells. We have developed the solid–in–oil nanodisperison technique to deliver pharmaceutical bioactives efficiently through the skin. Solid–in–oil nanodispersions are nanosized drug carriers designed to overcome the skin barrier. Drug administration using a patch is user–friendly and can improve patient compliance. Protein and peptide antigen drugs were efficiently delivered across the intact skin using the solid–in–oil nanodispersions. The technique is potent transcutaneous immunization method without needles.

DOI： 10.5360/membrane.48.25

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Organic and Biomolecular Chemistry  

Cytoplasm contains high concentrations of biomacromolecules. Protein behavior under such crowded conditions is reportedly different from that in an aqueous buffer solution, mainly owing to the effect of volume exclusion caused by the presence of macromolecules. Using a crosslinking reaction catalyzed by microbial transglutaminase (MTG) as a model, we herein systematically determined how the substrate size affects enzymatic activity in both dilute and crowded solutions of dextran. We first observed a threefold reduction in MTG-mediated crosslinking of a pair of small peptide substrates in 15 wt% dextran solution. In contrast, when proteinaceous substrates were involved, the crosslinking rates in 15 wt% dextran solutions accelerated markedly to levels comparable with the level in the absence of dextran. Our results provide new insights into the action of enzymes with regard to macromolecular substrates under crowded conditions, of which the potential utility was demonstrated by the formation of highly crosslinked protein polymers.

DOI： 10.1039/D2OB01549H

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記述言語：英語   出版者・発行元：Pharmaceutical Research  

Ionic liquids (ILs) have attracted growing interest as designer solvents/materials for exploring unrealized functions in many areas of research including drug formulations and delivery owing to their inherent tunable physicochemical and biological properties. The use of ILs in the pharmaceutical industry can address challenges related to the use of conventional organic solvent-based chemical permeation enhancers. Their tunability in forming ion pairs with a diverse range of ions enables the task-specific optimization of ILs at the molecular level. In particular, ILs comprising second- and third-generation cations and anions have been extensively used to design biocompatible drug delivery systems to address the challenges related to conventional topical and transdermal drug delivery, including limited permeability, high cytotoxicity, and skin irritation. This review highlights the progress in IL-related research with particular emphasis on the very recent conceptual developments in transdermal drug delivery. Technological advancement and approaches for the formation of IL-based topical and transdermal delivery systems, as well as their promising application in drug delivery, are also discussed.

DOI： 10.1007/s11095-022-03322-x

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記述言語：その他   掲載種別：研究論文（学術雑誌）   出版者・発行元：Molecular Pharmaceutics  

Fungal infections affect more than one billion people worldwide and cause more than one million deaths per year. Amphotericin B (AmB), a polyene antifungal drug, has been used as the gold standard for many years because of its broad antifungal spectrum, high activity, and low tendency of drug resistance. However, the side effects of AmB, such as nephrotoxicity and hepatotoxicity, have hampered its widespread use, leading to the development of a liposome-type AmB formulation, AmBisome. Herein, we report a simple but highly effective strategy to enhance the antifungal activity of AmBisome with a lipid-modified protein. The chitin-binding domain (LysM) of the antifungal chitinase, Pteris ryukyuensis chitinase A (PrChiA), a small 5.3 kDa protein that binds to fungal cell wall chitin, was engineered to have a glutamine-containing peptide tag at the C-terminus for the microbial transglutaminase (MTG)-catalyzed crosslinking reaction (LysM-Q). LysM-Q was site-specifically modified with a lysine-containing lipid peptide substrate of MTG with a palmitoyl moiety (Pal-K). The resulting palmitoylated LysM (LysM-Pal) exhibited negligible cytotoxicity to mammalian cells and can be easily anchored to yield LysM-presenting AmBisome (LysM-AmBisome). LysM-AmBisome exhibited a dramatic enhancement of antifungal activity toward Trichoderma viride and Cryptococcus neoformans, demonstrating the marked impact of displaying a cell-wall binder protein on the targeting ability of antifungal liposomal formulations. Our simple strategy with enzymatic protein lipidation provides a potent approach to upgrade other types of lipid-based drug formulations.

DOI： 10.1021/acs.molpharmaceut.2c00388

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記述言語：その他   掲載種別：研究論文（学術雑誌）   出版者・発行元：ACS Omega  

In this study, we present a highly stable vegetable oil ionic liquid (IL)-based emulsion liquid membrane (VOILELM) for the removal of lactic acid from water streams. The system developed as a part of this work comprises a non-ionic surfactant Span 80, sodium hydroxide as an internal stripping agent, sunflower canola oil as a green diluent, and IL-tetramethylammonium acetate [TMAm][Ac]-as a carrier. VOILELM stability was evaluated in terms of breakage, emulsion diameter, and standalone stability. The effect of various parameters, namely, concentration of the surfactant, concentration of the internal stripping agent, concentration of the carrier, phase ratio, homogenizer speed, and homogenization time, on the VOILELM stability was studied. The results revealed that VOILELM was highly stable, with 1.34% minimum breakage, 1.16 μm emulsion diameter, and 131 min standalone stability. The optimal process parameters were 0.1 wt % Span 80, 0.1 M NaOH, 0.3 wt % IL, 0.25 phase ratio, 5000 rpm homogenizer speed, and 5 min homogenization time. At these optimized conditions, 96.08% lactic acid extraction efficiency was achieved. Thus, a highly effective VOILELM was developed, with minimal breakage and emulsion diameter and maximum stability.

DOI： 10.1021/acsomega.2c03425

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記述言語：その他   掲載種別：研究論文（学術雑誌）   出版者・発行元：Journal of Bioscience and Bioengineering  

Amphotericin B (AMB) is a gold standard antifungal drug because of its broad-spectrum activity toward pathogenic yeasts and molds. Because of its low solubility in water and toxicity toward humans, several lipid-based formulations that either increase the aqueous solubility or decrease the side effects have been employed in practical use. In our previous research, we found that the combination of AMB with an artificial palmitoylated chitin-binding domain from Pteris ryukyuensis chitinase (LysM-Pal) resulted in synergistic antifungal action against Trichoderma viride. Herein, we prepared hybrid liposomal formulations by combining a commercially available AMB formulation and liposomes with different surface charges to explore key factors in the antifungal activity. The characterization of AMB-loaded liposomal formulations (AMB-LFs), including particle size distribution and zeta potential, showed that anionic and neutral AMB-LFs could stably encapsulate AMB. The combination of either anionic or neutral AMB-LFs with unmodified LysM decreased the minimum inhibitory concentration of AMB. The combination of neutral AMB-LF with LysM-Pal resulted in a further decrease in the MIC, up to 15-fold compared with that of the neutral AMB-LF alone. Our results demonstrate the potential utility of lipid-based liposomal formulations of AMB combined with lipid-modified proteinaceous binders to tackle fungal infections.

DOI： 10.1016/j.jbiosc.2022.06.005

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記述言語：英語   出版者・発行元：(公社)日本生物工学会  

市販のアンフォテリシンB(AMB)製剤と表面電荷が異なるリポソームを組合せてハイブリッドリポソーム製剤を調製し、抗真菌活性の重要な要因を探索した。AMB含有リポソーム製剤(AMB-LF)の粒子サイズ分布とゼータ電位を含む特性評価では、陰イオン性と中性のAMB-LFはAMBを安定的にカプセル化できた。アニオン性または中性AMB-LFと未修飾LysMの組合せではAMBのMICが低下した。中性AMB-LFとPteris ryukyuensisキチナーゼ由来の人工パルミトイル化キチン結合ドメインの組合せではMICは更に減少し、中性AMB-LF単独と比較して最大15倍になった。以上より、脂質修飾性蛋白質結合剤と組合せたAMBの脂質基盤リポソーム製剤の真菌感染に対する有用であると考えられた。

記述言語：その他   掲載種別：研究論文（学術雑誌）   出版者・発行元：Langmuir  

Protein palmitoylation, a post-translational modification, is universally observed in eukaryotic cells. The localization of palmitoylated proteins to highly dynamic, sphingolipid- and cholesterol-rich microdomains (called lipid rafts) on the plasma membrane has been shown to play an important role in signal transduction in cells. However, this complex biological system is not yet completely understood. Here, we used a combined approach where an artificial lipidated protein was applied to biomimetic model membranes and plasma membranes in cells to illuminate chemical and physiological properties of the rafts. Using cell-sized giant unilamellar vesicles, we demonstrated the selective partitioning of enhanced green fluorescent protein modified with a C-terminal palmitoyl moiety (EGFP-Pal) into the liquid-ordered phase consisting of saturated phospholipids and cholesterol. Using Jurkat T cells treated with an immunostimulant (concanavalin A), we observed the vesicular transport of EGFP-Pal. Further cellular studies with the treatment of methyl β-cyclodextrin revealed the cholesterol-dependent internalization of EGFP-Pal, which can be explained by a raft-dependent, caveolae-mediated endocytic pathway. The present synthetic approach using artificial and natural membrane systems can be further extended to explore the potential utility of artificially lipidated proteins at biological and artificial interfaces.

DOI： 10.1021/acs.langmuir.2c01205

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Nanoscale  

Single-walled carbon nanotubes (SWCNTs) emit photoluminescence (PL) in the near-infrared (NIR) region (>900 nm). To enhance their PL properties, defect doping via local chemical functionalization has been developed. The locally functionalized SWCNTs (lf-SWCNTs) emit red-shifted and bright E11* PL originating from the excitons localized at the defect-doped sites. Here, we observe the E11* PL energy shifts induced by protein adsorption via the avidin?biotin interactions at the doped sites of lf-SWCNTs. We establish that the difference in the structures of the avidin derivatives notably influences the energy shifts. First, lf-SWCNT-tethering biotin groups (lf-SWCNTs-b) are synthesized based on diazonium chemistry, followed by post-modification. The responsiveness of the lf-SWCNTs-b to different microenvironments is investigated, and a correlation between the E11* PL energy shift and the induction-polarity parameters of surrounding solvents is established. The adsorption of neutravidin onto the lf-SWCNTs-b induces an increase in the induction-polarity parameters around the biotin-doped sites, resulting in the red-shift of the E11* PL peak. The E11* PL shift behaviors of the lf-SWCNTs-b change noticeably when avidin and streptavidin are introduced compared to the case with neutravidin. This is due to the different microenvironments formed at the biotin-doped sites, attributed to the difference in the structural features of the introduced avidin derivatives. Moreover, we successfully enhance the detection signals of lf-SWCNTs-b (>three fold) for streptavidin detection using a fabricated film device. Therefore, lf-SWCNTs exhibit significant promise for application in advanced protein detection/recognition devices based on NIR PL.

DOI： 10.1039/D2NR01440H

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記述言語：その他   掲載種別：研究論文（学術雑誌）   出版者・発行元：ACS Omega  

Chemical dispersants are used extensively for oil spill remediation. Most of these dispersants are composed of a mixture of surfactants and organic solvents, which raises concerns about aquatic toxicity and environmental impact. In this study, the toxicity and biodegradability of an oil spill dispersant composed of the surface-active ionic liquid 1-butyl-3-methylimidazolium lauroyl sarcosinate [Bmim]-[Lausar] and Tween-80 were investigated. In addition, important environmental factors including salinity, temperature, and wave-mixing energy were optimized to obtain maximum dispersion effectiveness. The acute toxicity against zebrafish (Danio rerio) showed that the developed dispersant was practically non-toxic with a median lethal dose of more than 100 mg L-1 after 96 h. The dispersant also demonstrated outstanding biodegradability of 66% after 28 days. A model was developed using a response surface methodology that efficiently (R2 = 0.992) related the salinity, temperature, and wave-mixing energy of seawater to dispersion effectiveness. The system was then optimized, and a high dispersion effectiveness of 89.70% was obtained with an experimental error of less than 2%. Our findings suggest that the surface-active ionic liquid and Tween-80 mixture could be a viable alternative to toxic chemical dispersants for oil spill remediation.

DOI： 10.1021/acsomega.2c00752

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記述言語：日本語   出版者・発行元：公益社団法人 化学工学会  

<p>各種イオン液体，1-アルキル-3-メチルイミダゾリウムヘキサフルオロホスフェートおよび1-アルキル-3-メチルイミダゾリウムビス（トリフルオロメタンスルフォニル）イミドを輸送キャリアとして用いた乳化液膜による塩酸媒体からのロジウム（III）の抽出を行った．ロジウム（III）の抽出を促進するために，原料水溶液中にスズ（II）を添加し，ロジウムおよびスズの抽出挙動におよぼす各種操作条件の影響を検討した．各種金属の抽出速度は，イオン液体種，界面活性剤濃度，逆抽出剤濃度に大きく影響されることがわかった．イオン液体分子におけるアルキル鎖長並びに対アニオン部の構造の違いが抽出に影響をおよぼすことが示された．また，逆抽出剤として用いた2-アミノ-2-ヒドロキシメチル-1,3-プロパンジオールの存在量が多量のスズからのロジウムの選択的な抽出に影響をおよぼし，最適値が存在することが明らかとなった．本系における最適操作条件下において，迅速かつ定量的なロジウム抽出が達成された．</p>

DOI： 10.1252/kakoronbunshu.48.81

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記述言語：英語  

DOI： 10.1200/PO.21.00535

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ACS Infectious Diseases  

Combinations of antifungal drugs can have synergistic antifungal activity, achieving high therapeutic efficacy while minimizing the side effects. Amphotericin B (AMB) has been used as a standard antifungal drug for fungal infections; however, because of its high toxicity, new strategies to minimize the required dose are desirable. Chitinases have recently received attention as alternative safe antifungal agents. Herein, we report the combination of palmitoylated chitinase domains with AMB to enhance the antifungal activity. The chitin-binding domain (LysM) from Pteris ryukyuensis chitinase was site-specifically palmitoylated by conjugation reaction catalyzed by microbial transglutaminase. The palmitoylated LysM (LysM-Pal) exhibited strong antifungal activity against Trichoderma viride, inhibiting the growth completely at a concentration of 2 μM. This antifungal effect of LysM-Pal was mainly due to the effect of anchoring of palmitic acid motif to the plasma membrane of fungi. A combination of AMB with LysM-Pal resulted in synergistic enhancement of the antifungal activity. Intriguingly, LysM-Pal exhibited higher level of antifungal activity enhancement than palmitoylated catalytic domain (CatD) and fusion of LysM and CatD. Addition of 0.5 μM LysM-Pal to AMB reduced the minimal inhibition concentration of AMB to 0.31 μM (2.5 μM without LysM-Pal). The possible mechanism of the synergistic effect of AMB and LysM-Pal is destabilization of the plasma membrane by anchoring of palmitic acid and ergosterol extraction by AMB and destabilization of the chitin layer by LysM binding. The combination of LysM-Pal with AMB can drastically reduce the dose of AMB and may be a useful strategy to treat fungal infections.

DOI： 10.1021/acsinfecdis.2c00052

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：RSC Advances  

Chitosan adsorbents impregnated with a phosphonium-based ionic liquid (Chi_IL), trioctyldodecyl phosphonium chloride, were prepared for the adsorption of hexavalent chromium and compared to the performance of native chitosan. The physical and chemical properties of the adsorbents were characterized by Fourier-transform infrared spectroscopy, X-ray diffraction, scanning electron microscopy, and energy-dispersive X-ray spectroscopy. Effects of various parameters, such as pH, adsorbent dosage, contact time, temperature, and multi-component systems, were systematically examined. Chi_IL showed a high adsorption capacity (282.6 mg g?1) compared to native chitosan (238.1 mg g?1). The adsorption kinetics of the metals followed a pseudo-second-order kinetic model, and the experimental data were a good fit for the Freundlich isotherm model. Following the isotherm and activation energy parameter, adsorption of Cr(VI) onto Chi_IL follows a chemisorption process, possibly through an anionic exchange with the anion of the IL. The thermodynamic parameters suggested that the adsorption of Cr(VI) is a spontaneous and exothermic reaction. In the column adsorption, Chi_IL exhibited a longer column exhaustion time than that of native chitosan owing to the enhanced adsorption capacity caused by the introduction of IL. Moreover, the column with the parameters of 6 cm bed depth, 5 mL min?1 flow rate, and 50 mg L?1 was able to achieve the best performance in Cr(VI) adsorption.

DOI： 10.1039/D2RA00064D

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Solvent Extraction Research and Development, Japan  

In this study, we investigated an efficient recovery method of yttrium from a sulfuric acid leaching solution of spent Ni-MH battery electrode materials. In this newly proposed method, yttrium, one of the heavy rare earths (HREEs), was coprecipitated with light rare earths (LREEs) in the preliminary crude separation, and the residual yttrium was precisely recovered by solvent extraction using di-(2-ehylhexyl) phosphoric acid (D2EHPA) as the extractant. Yttrium in the leaching solution of 0.7 g/L that remained at 0.2 g/L after the coprecipitation operation; however, it could be reduced to 0.001 ? 0.002 g/L by the solvent extraction process in the following step. In this technical report, we focused on the solvent extraction operation. The extractant, D2EHPA, has a high affinity for yttrium, and we confirmed the possibility of improving the recovery yield of yttrium from 43% by coprecipitation alone to 98% by introducing solvent extraction.

DOI： 10.15261/serdj.29.79

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Hydrometallurgy  

The recycling of nickel, cobalt and rare earths from spent nickel?metal-hydride batteries was investigated. Nickel and cobalt were recovered as a nickel?cobalt mixed sulfide, which can be used as an intermediate raw material in existing nickel refineries. Rare earths were recovered as double sulfates, which can be recycled into industrial materials. In the recovery of rare earths, yttrium, a heavy rare earth, could be precipitated and recovered by co-precipitation with a light rare-earth double sulfate, which was considered impossible by the double-sulfate precipitation method because of high solubility of yttrium double sulfate. On the other hand, the coprecipitation behavior of yttrium was found to be unstable at the pilot scale because the stirring force was weaker than that in the laboratory experiments. In this study, the optimum conditions for leaching, double-sulfate precipitation, and sulfide precipitation reactions were determined in a laboratory test and the good performance was demonstrated in a pilot test. Based on the results, the estimated metal yields were 87% nickel, 90% cobalt, 54% yttrium, 99% lanthanum and 99% cerium. The nickel and cobalt impurities in the double sulfate that were recovered by this process were 0.04% and 0.005%, respectively, and the rare-earth impurities in the nickel?cobalt mixed sulfide were low at 0.049% yttrium, 0.007% lanthanum and 0.003% cerium. This process combined with a precipitation method showed a high separation performance.

DOI： 10.1016/j.hydromet.2022.105826

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Journal of Molecular Liquids  

Salicylic acid is an important component in cosmetics and skincare products and is widely found in aqueous streams as waste material. The present study reported the extraction of salicylic acid from wastewaters using a new technique termed as ‘ionic liquid-based emulsion liquid membrane’ (IL-ELM). Ionic liquids were introduced as carriers in IL-ELMs to enhance the emulsion stability. COSMO-RS simulation tool was employed to identify the effective IL among the 45 ILs composed of different cations and anions. It was found that IL [TMAm][Cl] (tetramethylammonium chloride) was found to be the most effective extracting agent for the extraction of salicylic acid that possesses the higher capacity, selectivity and lower activity coefficient towards analyte molecules. The COSMO-RS prediction results were in good agreement with the experimental data. Furthermore, this study optimized several operating conditions, including surfactant concentration, stripping agent concentration, IL concentration, emulsification time, homogenization speed and extraction time that affected the extraction efficiency. Overall, the proposed IL-ELM showed 90.04% extraction efficiency for salicylic acid under the optimized conditions of 0.005?M NaOH as stripping agent, 1.0?wt% Span-20 as emulsifier, 0.2?wt% [TMAm][Cl], 4000?rpm homogenization speed, 3:1 treat ratio and 25?min of extraction time.

DOI： 10.1016/j.molliq.2021.118280

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Chemical Communications  

Pairs of peptide amphiphiles with immiscible hydrophobic tails were synthesized and their assembly formation was investigated. These pairs formed self-sorting supramolecular fibres using a standard heating?cooling protocol, while one pair with longer hydrophobic tails formed a co-assembly when an additional heating process was applied.

DOI： 10.1039/d1cc05560g

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記述言語：その他   掲載種別：研究論文（学術雑誌）   出版者・発行元：Journal of Molecular Liquids  

Cellulose nanocrystals (CNCs) have attracted a great interest for various industrial applications due to their wide range of characteristics including compatibility, recyclability, and reproducibility. The efficient preparation of the quality cellulose nanocrystals (CNCs) from microcrystalline cellulose (MCC) utilizing ionic liquid (IL) 1-butyl-3-methylimidazoluim hydrogen sulfate ([Bmim][HSO4]) and dimethyl sulfoxide (DMSO) binary mixture was investigated and compared the results with those obtained from the pure IL. The produced CNCs were characterized using atomic force microscopy (AFM), Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA) and x-ray diffractometry (XRD). It was observed that the average diameter of CNCs obtained with IL-cosolvent (C-CNCs), and pure IL (P-CNCs) were 50 nm and 0.77 ?m, respectively, whereas the length of C-CNCs and P-CNCs were found to be 757 nm and 2.11 ?m, respectively. The non-isothermal Coats-Redfern model with numerous mechanisms were used to model the thermal degradation kinetics of CNCs. The C-CNCs and P-CNCs exhibited lower activation energies of 86.45 and 19.10 KJ/mol respectively, than that of MCC 386.8 KJ/mol. The role of DMSO in the production of CNCs was discussed. The proposed IL based binary mixture could be an effective for the production of high quality CNCs for different applications.

DOI： 10.1016/j.molliq.2021.118208

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記述言語：日本語   出版者・発行元：公益社団法人 日本油化学会  

<p>タンパク質や核酸などのバイオ分子は医薬品として利用され，臨床現場で大きな成果をあげるようになった。経皮吸収とは薬を皮膚から送達する方法であり，注射投与と比較して，安全かつ簡便な方法であることから，バイオ分子を経皮吸収させるための技術開発が注目されている。バイオ分子を油中にナノメートルサイズの粒子として分散させるSolid-in-Oil（S/O）技術は，経皮吸収促進効果をもつ油状基剤とバイオ分子を組み合わせることができることから，バイオ分子の経皮吸収において非常に有効であることが知られており，インスリンのようなタンパク質の経皮吸収効率の向上が報告されている。近年では，塗り薬型ワクチンの開発などが盛んに研究されており，抗原特異的な抗体産生や細胞性免疫の誘導が可能であることが明らかとなっている。今後の発展によって，S/O技術によるバイオ分子の経皮吸収製剤が実用化されることが期待される。</p>

DOI： 10.5650/oleoscience.22.121

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記述言語：その他   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.cocis.2021.101515

記述言語：その他   掲載種別：研究論文（学術雑誌）  

Lipidic cubic phase (LCP) is a self-assembled system composed of lipids with interpenetrated aqueous channels, and its potential in drug delivery systems has been investigated. Although LCP was shown to improve transcutaneous penetration of hydrophilic molecules of up to 1203 Da so far, the transcutaneous delivery of larger molecules such as proteins has not been achieved. This is likely because proteins are usually larger than the aqueous channels of LCP (∼37.2 Å in diameter), which limits the molecular diffusion in LCP. In this report, we overcome this issue by adding N-octyl-β-d-glucopyranoside to glyceryl monooleate-water-based LCP to give swollen LCP (SLCP), which has larger aqueous channel diameters (∼65.6 Å). First, we systemically evaluated the effect of swelling on drug diffusion in LCP/SLCP. The release kinetics of various peptides and proteins whose sizes ranged from 9.14 to 55.28 Å in diameter were evaluated, and the diffusion coefficients (D) were calculated by the Fickian diffusion model. As expected, all peptides and proteins diffused faster in SLCP than in LCP. A more detailed analysis revealed a negative linear relationship between log D and the ratio of the radius of gyration of the proteins to the aqueous channel radius, indicating that swelling of a cubic nanostructure is an effective strategy to enhance D. Next, the skin penetration of proteins encapsulated in LCP and SLCP was evaluated. The skin penetration of ovalbumin (42.9 kDa), for example, was enhanced by SLCP but not by LCP, and a positive correlation between D and the amount of skin penetration was found. Collectively, this study provides an effective measure for designing LCP systems that enhance transcutaneous penetration of biomacromolecules.

DOI： 10.1021/acsami.1c16659

記述言語：その他   掲載種別：研究論文（学術雑誌）  

Oral delivery of the sparingly soluble drug methotrexate (MTX) is challenging owing to its poor bioavailability and low solubility. To address this challenge, the present study reports the conversion of MTX into a series of five ionic liquids (ILs) comprising a cationic component—i.e., cholinium (Cho), tetramethylammonium (TMA), tetrabutylphosphonium (TBP), or an amino acid ester—and an anionic component—i.e., MTX. The biocompatibility, pharmacokinetics, tissue distribution, and antitumor efficacy of each MTX-based IL were investigated to determine its usefulness as a pharmaceutical. Oral administration to mice revealed that proline ethyl ester MTX (IL[ProEt][MTX]) had 4.6-fold higher oral bioavailability than MTX sodium, followed by aspartic diethyl ester MTX, IL[TBP][MTX], IL[Cho][MTX], and IL[TMA][MTX]. The peak plasma concentration, elimination half-life, area under the plasma concentration, mean absorption time, and body clearance of IL[ProEt][MTX] were significantly (p < 0.0001) higher by 1.7-, 6.2-, 4.6-, 2.5-, and 3.6-fold, respectively, than those of MTX sodium. MTX accumulation in the lungs, spleen, kidney, and gastrointestinal tract was also reduced by 5.6-, 1.8-, 1.5-, and 1.4-fold, respectively, indicating the IL formulations had lower systemic toxicity than free MTX. Mechanistic studies revealed that the IL[ProEt][MTX] solution formed spherical structures with an average size of 190 nm. This was probably responsible for its improved oral absorption performance in vivo. In vivo antitumor studies also demonstrated that IL[ProEt][MTX] suppressed tumor growth more than MTX sodium. These results suggest that MTX-based ILs provide a simple scalable approach to improving the oral bioavailability of poorly soluble MTX.

DOI： 10.1016/j.ijpharm.2021.121129

記述言語：その他   掲載種別：研究論文（学術雑誌）  

Since injection administration for diabetes is invasive, it is important to develop an effective transdermal method for insulin. However, transdermal delivery remains challenging owing to the strong barrier function of the stratum corneum (SC) of the skin. Here, we developed ionic liquid (IL)-in-oil microemulsion formulations (MEFs) for transdermal insulin delivery using choline-fatty acids ([Chl][FAs])—comprising three different FAs (C18:0, C18:1, and C18:2)—as biocompatible surface-active ILs (SAILs). The MEFs were successfully developed using [Chl][FAs] as surfactants, sorbitan monolaurate (Span-20) as a cosurfactant, choline propionate IL as an internal polar phase, and isopropyl myristate as a continuous oil phase. Ternary phase behavior, dynamic light scattering, and transmission electron microscopy studies revealed that MEFs were thermodynamically stable with nanoparticle size. The MEFs significantly enhanced the transdermal permeation of insulin via the intercellular route by compromising the tight lamellar structure of SC lipids through a fluidity-enhancing mechanism. In vivo transdermal administration of low insulin doses (50 IU/kg) to diabetic mice showed that MEFs reduced blood glucose levels (BGLs) significantly compared with a commercial surfactant-based formulation by increasing the bioavailability of insulin in the systemic circulation and sustained the insulin level for a much longer period (half-life > 24 h) than subcutaneous injection (half-life 1.32 h). When [Chl][C18:2] SAIL-based MEF was transdermally administered, it reduced the BGL by 56% of its initial value. The MEFs were biocompatible and nontoxic (cell viability > 90%). They remained stable at room temperature for 3 months and their biological activity was retained for 4 months at 4 °C. We believe SAIL-based MEFs will alter current approaches to insulin therapy and may be a potential transdermal nanocarrier for protein and peptide delivery.

DOI： 10.1021/acsami.1c11533

記述言語：英語   掲載種別：研究論文（学術雑誌）  

An efficient recovery of lithium (Li(I)) from salt lakes is currently a challenging issue. Herein, we report a feasible extraction of Li(I) from a simulated salt lake solution using a novel extraction system, in which a functionalized ionic liquid (FIL) is dissolved in a different ionic liquid diluent. As a functional extractant, 3-methyl-1-octylimidazolium thenoyltrifluoroacetone [Omim][TTA] was successfully prepared in a simple way and its extraction performance for Li(I) was evaluated. The effects of pH and metal concentration on extraction, as well as the stripping property, were systematically investigated. It was found that the FIL could effectively act as the extractant of Li(I) over a wide range of pH, and even under acidic conditions. The extraction ability of the FIL was markedly enhanced by its use in an ionic liquid diluent. The obtained results demonstrated that Li(I) was extracted from the aqueous solution into the ionic liquids with a high extraction efficiency even in a five-cycle reusability test. Furthermore, using a simulated salt lake solution, Li(I) was selectively extracted with a high separation factor of 227 over Na(I), whereas Na(I) and K(I) remained in the aqueous feed solution.

DOI： 10.1016/j.desal.2021.115073

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Enzymatic reaction offers site-specific conjugation of protein units to form protein conjugates or protein polymers with intrinsic functions. Herein, we report horseradish peroxidase (HRP)- and microbial transglutaminase (MTG)-catalyzed orthogonal conjugation reactions to create antifungal protein polymers composed of Pteris ryukyuensis chitinase-A (ChiA) and its two domains, catalytic domain, CatD, and chitin-binding domain, LysM2. We engineered the ChiA and CatD by introducing a peptide tag containing tyrosine (Y-tag) at N-termini and a peptide tag containing lysine and tyrosine (KY-tag) at C-termini to construct Y-ChiA-KY and Y-CatD-KY. Also, LysM2 with Y-tag and KY-tag (Y-LysM2-KY) or with a glutamine-containing peptide tag (Q-tag) (LysM2-Q) were constructed. The proteins with Y-tag and KY-tag were efficiently polymerized by HRP reaction through the formation of dityrosine bonds at the tyrosine residues in the peptide tags. The Y-CatD-KY polymer was further treated by MTG to orthogonally graft LysM2-Q to the KY-tag via isopeptide formation between the side chains of the glutamine and lysine residues in the peptide tags to form LysM2-grafted CatD polymer. The LysM2-grafted CatD polymer exhibited significantly higher antifungal activity than the homopolymer of Y-ChiA-KY and the random copolymer of Y-CatD-KY and Y-LysM2-KY, demonstrating that the structural differences of artificial chitinase polymers have a significant impact on the antifungal activity. This strategy of polymerization and grafting reaction of protein can contribute to the further research and development of functional protein polymers for specific applications in various fields in biotechnology.

DOI： 10.1021/acs.bioconjchem.1c00235

記述言語：その他   掲載種別：研究論文（学術雑誌）  

Lipid-based biocompatible ionic liquids (LBILs) have attracted attention as carriers in transdermal drug delivery systems (TDDSs) because of their lipophilic character. In this study, we report the formulation of a peptide-LBIL complex microencapsulated in an oil phase as a potential carrier for the transdermal delivery of leuprolide acetate as a model hydrophilic peptide. The peptide-LBIL complexes were prepared via a water-in-oil emulsion composed of 1,2-dimyristoyl-sn-glycerol-3-ethyl-phosphatidylcholine (EDMPC), a fatty acid (stearic, oleic, and linoleic acid)-based LBIL, and cyclohexane followed by freeze-drying to remove the water and cyclohexane. Then, the peptide-LBIL complexes were nanodispersed and stabilized in isopropyl myristate (IPM) using sorbitol laurate (Span-20). Ionic-liquid-in-oil nanodispersions (IL/O-NDs) were prepared with varying weight ratios of LBILs and Span-20 as the surfactant and the cosurfactant, respectively. Keeping the overall surfactant constant at 10 wt % in IPM, a 5:5 wt % ratio of surfactant (IL) and cosurfactant (Span-20) in the IL/O-NDs significantly (p < 0.0001) increased the physiochemical stability, drug-loading capacity, and drug encapsulation efficiency. The in vitro and in vivo peptide delivery across the skin was increased significantly (p < 0.0001) using IL/O-NDs, compared with non-IL-treated groups. Of all of the LBIL-based formulations, [EDMPC][Linoleate]/O-ND was considered the most preferable for a TDDS based on the pharmacokinetic parameters. The transdermal delivery flux with [EDMPC][Linoleate]/O-ND was increased 65-fold compared with the aqueous delivery vehicle. The IL/O-NDs were able to deform the lipid and protein arrangements of the skin layers to enhance the transdermal permeation of the peptide. In vitro and in vivo cytotoxicity studies of the IL/O-NDs revealed the biocompatibility of the LBIL-based formulations. These results indicated that IL/O-NDs are promising biocompatible carriers for lipid-peptide TDDSs.

DOI： 10.1021/acsabm.1c00563

記述言語：その他   掲載種別：研究論文（学術雑誌）  

Coronavirus disease 2019 (COVID-19) has spread across the world, and no specific antiviral drugs have yet been approved to combat this disease. Favipiravir (FAV) is an antiviral drug that is currently in clinical trials for use against COVID-19. However, the delivery of FAV is challenging because of its limited solubility, and its formulation is difficult with common organic solvents and water. To address these issues, four FAV ionic liquids (FAV-ILs) were synthesized as potent antiviral prodrugs and were fully characterized by nuclear magnetic resonance (NMR) spectroscopy, Fourier-transform infrared (FT-IR) spectrometry, powder X-ray diffraction (PXRD), thermogravimetric analysis (TGA), derivative thermogravimetry (DTG), and differential scanning calorimetry (DSC). The aqueous solubility and in vivo pharmacokinetic properties of the FAV-ILs were also evaluated. The FAV-ILs exhibited improved aqueous solubility by 78 to 125 orders of magnitude when compared with that of free FAV. Upon oral dosing in mice, the absolute bioavailability of the β-alanine ethyl ester FAV formulation was increased 1.9-fold compared with that of the control FAV formulation. The peak blood concentration, elimination half-life, and mean absorption time of FAV were also increased by 1.5-, 2.0-, and 1.5-fold, respectively, compared with the control. Furthermore, the FAV in the FAV-ILs exhibited significantly different biodistribution compared with the control FAV formulation. Interestingly, drug accumulation in the lungs and liver was improved 1.5-fold and 1.3-fold, respectively, compared with the control FAV formulation. These results indicate that the use of ILs exhibits potential as a simple, scalable strategy to improve the solubility and oral absorption of hydrophobic drugs, such as FAV.

DOI： 10.1021/acs.molpharmaceut.1c00324

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Spent automotive catalysts (SACs) are the most abundant secondary source of platinum group metals (PGMs), but the recycling of these materials is quite challenging. In the present study, we assessed the recovery of Pt, Pd, and Rh from a SAC leachate solution using polymer inclusion membranes (PIMs) containing the ionic liquid trioctyl (dodecyl) phosphonium chloride (P88812Cl). After pretreatment of the SAC using a reducing agent, metals could be extracted using relatively dilute acid solutions. The selective transport of PGMs from such solutions was demonstrated with two types of membranes having the same chemical composition: an isotropic dense membrane (ID-PIM) and an anisotropic porous membrane (AP-PIM). Using the ID-PIM, more than 90% of Pt and Pd in the SAC extraction solutions could be recovered with remarkably high purity. In contrast, the AP-PIM could recover Pt, Pd, and Rh in reasonable yields and purities with dramatically faster transport kinetics. Both membrane types demonstrated excellent durability with no loss of carrier molecules over a 10-day exposure to various harsh chemicals.

DOI： 10.1016/j.memsci.2021.119296

記述言語：その他   掲載種別：研究論文（学術雑誌）  

DOI： 10.1021/acs.bioconjchem.1c00027

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Enzymes play a central role in the detection of target molecules in biotechnological fields. Most probes used in detection are bifunctional proteins comprising enzymes and binding proteins conjugated by chemical reactions. To create a highly sensitive detection probe, it is essential to increase the enzyme-to-binding protein ratio in the probe. However, if the chemical reactions required to prepare the probe are insufficiently site-specific, the detection probe may lose functionality. Genetic modifications and enzyme-mediated post-translational modifications (PTMs) can ensure the site-specific conjugation of proteins. They are therefore promising strategies for the production of detection probes with high enzyme contents, i.e., polymeric bifunctional proteins. Herein, we review recent advances in the preparation of bifunctional protein conjugates and polymeric bifunctional protein conjugates for detection. We have summarized research on genetically fused proteins and enzymatically prepared polymeric bifunctional proteins, and will discuss the potential use of protein polymers in various detection applications.

DOI： 10.2116/analsci.20SCR07

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Seven new amide-functionalised phosphonium-based ionic liquids (APILs) with chloride anions are synthesised and applied to extraction of rhodium(iii) from HCl solution. The effects of structural modification of the APILs on the extraction performance are examined by liquid-liquid extraction using toluene as a diluent and the results compared with those for trihexyltetradecylphosphonium chloride ([P-66614][Cl]), a typical commercial extractant. The performance of the APILs as rhodium(iii) extractants is influenced by three main factors: (1) the length of the alkyl chains attached to the P atom; (2) the length of the linker between the amide and phosphonium moiety; and (3) the type of amide group. A novel ligand, [3 degrees C2P444][Cl], had outstanding performance in the effective recovery of rhodium(iii). Extraction of rhodium(iii) from a 1.0 mol dm(-3) HCl solution with 0.5 mol dm(-3) [3 degrees C2P444][Cl] proceeded quantitatively (>98%) and the extraction efficiency was higher than that of the commercial extractant [P-66614][Cl]. The mechanism of rhodium(iii) extraction by [3 degrees C2P444][Cl] was investigated by slope analysis, UV-vis, and FT-IR spectroscopy. These results indicate that [RhCl4(H2O)(2)](-) in aqueous solution is extracted by [3 degrees C2P444][Cl] through an anion-exchange mechanism and slowly converted into a dimer, [Rh2Cl9](3-), in the organic phase.

DOI： 10.1039/d1ra00489a

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Supramolecular fibrous materials in biological systems play important structural and functional roles, and therefore, there is a growing interest in synthetic materials that mimic such fibrils, especially those bearing enzymatic reactivity. In this study, we investigated the self-assembly and enzymatic post-modification of short aromatic peptide amphiphiles (PAs), Fmoc-LnQG (n = 2 or 3), which contain an LQG recognition unit for microbial transglutaminase (MTG). These aromatic PAs self-assemble into fibrous structures via π-π stacking interactions between the Fmoc groups and hydrogen bonds between the peptides. The intermolecular interactions and morphologies of the assemblies were influenced by the solution pH because of the change in the ionization states of the C-terminal carboxy group of the peptides. Moreover, MTG-catalyzed post-modification of a small fluorescent molecule bearing an amine group also showed pH dependency, where the enzymatic reaction rate was increased at higher pH, which may be because of the higher nucleophilicity of the amine group and the electrostatic interaction between MTG and the self-assembled Fmoc-LnQG. Finally, the accumulation of the fluorescent molecule on these assembled materials was directly observed by confocal fluorescence images. Our study provides a method to accumulate functional molecules on supramolecular structures enzymatically with the morphology control.

DOI： 10.3390/ijms22073459

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Hydrophobic deep eutectic solvents (DESs) have attracted much attention as sustainable extraction media for various metals. However, in previously developed DESs, only one DES component is involved in metal complex formation, which has limited their extraction performance and selectivity. Here, we propose a novel synergistic DES concept for improving the performance of environmentally benign liquid-liquid extraction of lithium (Li). Two different conventional extractants, a beta-diketone and a neutral extractant, were effective for creating the synergistic DESs. When the two extractants were mixed, they formed a liquid DES. DESs have much lower viscosity than conventional hydrophobic ionic liquids. The Conductor-like Screening Model for Real Solvents method was used to estimate the formation of DESs with the melting point depressed by the intermolecular interaction between their components. The extraction performance of Li was greatly enhanced with the synergistic DESs. The extraction capacity of Li reached 4.4 g/L using the optimum DES combination because it was solvent-free and highly concentrated. Using the optimum DES, highly selective recovery of Li over Na and K was demonstrated with a model brine solution. This is the first report of efficient and selective extraction of Li with DES-based liquid-liquid extraction.

DOI： 10.1021/acssuschemeng.0c07606

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1038/s41598-020-63362-4

記述言語：その他   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.ejps.2020.105521

記述言語：その他   掲載種別：研究論文（学術雑誌）  

Surface-active ionic liquid (SAIL) surfactants have attracted attention as promising alternatives to conventional surfactants because of their tailor-made and tunable properties. SAILs also address the limitations associated with conventional surfactants including toxicity and formation of unstable micelles. Here, we investigated the aggregation behavior of three biocompatible choline N-lauroyl-amino acid (NLAA)-based ILs with different amino acid side chains in aqueous solutions. The micellar behaviors of NLAA-ILs were investigated using surface tensiometry, conductometry, dynamic light scattering (DLS) and transmission electron microscopy (TEM). The critical micellar concentration (CMC) of the NLAA-ILs was found to be 2 to 4-fold lower compared with the conventional surfactant sodium dodecyl sulfate (SDS). The thermodynamic behavior confirmed that the micelle formation of NLAA-ILs was stable, spontaneous and entropy driven at room temperature. DLS and TEM studies revealed that the size and shape of the micelles depended on the presence of an N‑hydrogen group in the head group of the anion. Choline N-lauroyl glycinate ([Cho][NLG]) and dicholine N-lauroyl aspartate ([Cho]2[NLA]) were predominantly produced as unilamellar vesicles in water whereas choline N-lauroyl sarcosinate ([Cho][NLS]) formed small spherical micelles. Importantly, SAIL [Cho][NLG] showed lower toxicity toward mammalian cells compared with the analogous ILs or the conventional surfactant SDS and similar toxicity to the conventional surfactant Tween 80. SAIL [Cho][NLG] was more efficient at forming hydrophobic ion pairs with the macromolecular drug heparin compared with SAIL [Cho][NLS]. These results clearly suggest that the biocompatible NLAA-ILs represent promising potential substitutes for conventional surfactants in various biomedical applications.

DOI： 10.1016/j.molliq.2020.114424

記述言語：その他   掲載種別：研究論文（学術雑誌）  

Hydrogels possessing the ability to control cell functions have great potential as artificial substrates for cell culture. Herein, we report dual-functionalizable protein-polymer hybrid hydrogels prepared by thiol oxidation catalyzed by horseradish peroxidase and a phenolic molecule. A chimera protein of streptavidin (SA) and the SpyCatcher protein, with a cysteine residue at its N-terminus, (C-SA-SC) was constructed and co-cross-linked with thiol-functionalized four-arm polyethylene glycol (PEG-SH) to obtain hydrogels possessing two orthogonal conjugation moieties. Hydrogel formation using C-SA-SC conjugated with biotinylated or SpyTagged functional molecules (premodification strategy) resulted in the formation of hydrogels with a uniform distribution of the functional molecules. Postmodification of the functional molecules of the C-SA-SC hydrogel with biotin or SpyTag could alter the three-dimensional (3D) spatial distribution of the functional molecules within the hydrogels depending on the mode of conjugation (SA/biotin or SpyCatcher/SpyTag), the size of the functional molecules, and the length of time of the modification. NIH-3T3 cells cultured on a C-SA-SC hydrogel, dual-functionalized with a biotinylated-Arg-Gly-Asp-Ser (RGDS) peptide and a basic fibroblast growth factor (bFGF) with SpyTag, showed cell adhesion to the PEG-SH-based hydrogels and cell morphological changes in response to the immobilized RGDS peptide and the bFGF. Moreover, the cells showed higher proliferation on the dual-functionalized C-SA-SC hydrogel than the cells cultured on hydrogels without either the RGDS peptide or the bFGF, demonstrating the benefits of dual-functionalizable hydrogels. The C-SA-SC hydrogel presented in this study is capable of being orthogonally functionalized by two different functional molecules with different 3D distributions of each molecule within the hydrogel and thus has the potential for use as a cell culturing scaffold for creating artificial cellular microstructures.

DOI： 10.1021/acsabm.0c00940

記述言語：英語   掲載種別：研究論文（学術雑誌）  

We report a new series of lipid-based biocompatible ionic liquids (LBILs) consisting of the long-chain phosphonium compound 1,2-dimyristoyl-sn-glycero-3-ethyl-phosphatidylcholine as the cation and the long-chain fatty acids stearic acid, oleic acid, or linoleic acid as anions. These materials were found to be completely miscible with many polar and nonpolar organic solvents as well as dispersible in water. These LBILs also exhibited excellent biocompatibility with an artificial three-dimensional human epidermis model.

DOI： 10.1039/d0cc04491a

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.jbiosc.2020.05.010

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Ionic liquids (ILs) attract significant attention as novel solvents for drug delivery systems because of their ability to solubilize poorly soluble drugs and tune the physiological properties of active pharmaceutical ingredients. For the next generation of IL-based drug delivery systems, biocompatibility is a high priority. In the current study, choline-fatty acids ([Cho][FA]) were used as a biocompatible IL to mediate the dissolution of a water-soluble antigen peptide in an oil-based skin penetration enhancer. Among the candidate fatty acids (C8, C10, C12, C14, C16, C18:0, and C18:1), C18:1 was selected because of its low cytotoxicity and mediation of skin permeability for an antigen peptide. Using IL[Cho][C18:1] and an oil-based penetration enhancer, the flux of transdermal delivery of the peptide increased 28-fold compared with delivery using an aqueous vehicle. Furthermore, the IL-mediated transcutaneous vaccination succeeded in suppressing tumor growth in vivo compared to injection. The skin irritation produced by this formulation was tested using an in vitro 3D constructed skin tissue model and an in vivo histological study, which concluded that the formulation did not cause skin irritation. The results suggest that biocompatible IL-mediated dissolution in an oil-based skin penetration enhancer is a promising strategy for transdermal drug delivery.

DOI： 10.1021/acs.molpharmaceut.0c00598

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： https://doi.org/10.1021/acsabm.0c00940

記述言語：その他   掲載種別：研究論文（学術雑誌）  

Ionic liquid (IL)-based drug delivery systems have attracted considerable interest owing to their intrinsic tunability and ability to transport small or large molecules through the skin. However, the development of "green"ILs remains challenging. Herein, eight potentially "green"fatty acid-based amino acid ILs (FAAAE-ILs) were synthesized, and their potency in transdermal drug delivery was investigated using ibuprofen and a peptide drug. The synthesized ILs were characterized to evaluate their physicochemical, thermal, and biological (cytotoxicity) properties. The in vitro skin permeability of the synthesized FAAAE-ILs was evaluated through pig skin. All of the FAAAE-ILs are liquid at room temperature and freely miscible with pharmaceuticals-permitted solvents/agents (e.g., isopropyl myristate (IPM), Span-20, and DMSO). In vitro cytotoxicity study showed that the cell viability of all FAAAE-ILs (10% in IPM) was at least 10 times lower than that for a conventional chemical permeation enhancer (CPE), sodium lauryl sulfate. FAAAE-ILs facilitated excellent ibuprofen solubility through multiple hydrogen bonding interactions between the drug and the ILs. An in vitro permeation study showed that the FAAAE-ILs were more effective in enhancing the permeability of drug molecules than the conventional CPE transcutol. The linoleate-based ILs showed a higher degree of permeation than the oleate-based ILs. Among the linoleate-based ILs and ibuprofen formulations (drug in 10% IL in IPM), the l-proline ethyl ester linoleate ([l-ProEt][Lin])-based formulation exhibited best results, followed by β-alanine ethyl ester linoleate, d-proline ethyl ester linoleate, and l-leucine ethyl ester linoleate after 48 h. Interestingly, the same FAAAE-IL ([l-ProEt][Lin])-containing formulation showed significant enhancement of peptide penetration across pig skin compared with CPE-containing formulations (10% in IPM). The results demonstrate that the FAAAE-IL is a promising green alternative to conventional CPEs for the transdermal delivery of small and large therapeutic molecules.

DOI： 10.1021/acssuschemeng.0c03419

記述言語：英語   掲載種別：研究論文（学術雑誌）  

The recovery of scarce metals from secondary resources is desirable from an economic and ecological perspective. The limitations of natural resources and the continuous growth of advanced metal materials increase the importance of securing metal resources. The purpose of this study was to utilize a newly synthesized ionic liquid (IL), trioctyldodecylphos-phonium bromide (P8,8,8,12Br), as a novel extractant for Cd(II) and Zn(II) from a chloride medium. An investigation into the extraction parameters, including the acid concentration, extractant type, and equilibration time, for both metals was performed. Two IL molecules were involved in the extraction reaction for both metals. The selective stripping of Cd(II) and Zn(II) from the loaded IL phase was achieved with 1 M oxalic acid and 3M HNO3, respectively. The presence of other metals did not affect the extraction efficiencies of Cd(II) and Zn(II). The extraction efficiencies of Cd(II) and Zn(II) were maintained at 94% and 95%, respectively, with an equilibration time of 2 h. Although Fe(III) and Cu(II) were extracted into the IL phase in significant amounts, the removal of Fe(III) and COI) could be achieved by scrubbing using 1 M Na2SO3 and 3 M H2SO4, respectively. P8,8,8,12Br exhibited excellent recyclability through consecutive extraction-stripping cycles. A recovery scheme for Cd(II) and Zn(II) from a wasted battery-model solution was developed based on the extraction data. P8,8,8,12Br could recover Cd(II) and Zn(II) from a mixed metal solution in high purity. This study highlights the future potential of P8,8,8,12Br in metal recycling.

DOI： 10.1252/jcej.20we030

記述言語：その他   掲載種別：研究論文（学術雑誌）  

DOI： 10.3390/pharmaceutics12090814

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Mutual separation of platinum group metals (PGMs) is a particularly challenging issue in metal recovery technology. In this study, we report the successful separation of Pt(IV), Pd(II), and Rh(III) by sequential transport through polymer inclusion membranes (PIMs) containing the ionic liquid trioctyl(dodecyl) phosphonium chloride (P88812CI) as a metal carrier. This study describes the screening of suitable receiving solutions, optimization of the operating conditions, establishing a possible transport mechanism, and evaluation of the membrane stability. In the first transport sequence, Pt(IV) was selectively transported into the receiving solution with a recovery of >95%, while Pd(II) and Rh(III) remained in the feed solution. In the second transport sequence, high-purity Pd(II) was transported into the receiving solution with a recovery of >95%, while Rh(III) remained completely in the feed solution. Furthermore, the PIM exhibited a stable performance with multiple uses over a 4-week period during which four Pt(IV) and Pd(II) sequential transport cycles were continuously carried out.

DOI： 10.1021/acssuschemeng.0c03205

記述言語：その他   掲載種別：研究論文（学術雑誌）  

Biofunctional hydrogels prepared by a peroxidase, especially horseradish peroxidase (HRP), serve as an excellent class of materials or platform for the development of cellular scaffolds because their biocompatibility and mild and tunable reaction conditions provide them with desirable properties. In this focus review, we summarize our decade of research into HRP-mediated fabrication of biofunctional hydrogels and their applications, in particular cell culture scaffolds. A brief overview of potential substrates employed in HRP and improvement of the HRP hydrogelation system from the initial step until the hydrogen peroxide removal stage in an effort to meet environmental standards is discussed. We highlight our system and describe its biocompatibility and ability to functionalize molecules to support biofabrication by increasing cellular adhesiveness, retaining growth factor affinity, and finally accelerating the formation of two- and three-dimensional multicellular architectures. In the last section, we outline the adoption of hydrogelation as a self-standing, compartmentalized reaction system, i.e., the use of hydrogel marble to conduct cell-free biosynthesis. We believe that this HRP-mediated hydrogel system offers great potential not only as a cell culture scaffold but also for various biomedical applications.

DOI： 10.1038/s41428-020-0344-7

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Emulsion liquid membrane (ELM) is an effective way to recover and remove biologically active compounds, particularly drug molecules from hospital wastewater. Ionic liquid (IL)-assisted ELMs have recently been found to be efficient for recovery and removal of biologically active compounds owing to their excellent characteristics. However, the selection of potential ILs from the wide range of anion-cation combinations is quite challenging. To address this issue, the conductor-like screening model for real solvents (COSMO-RS) has emerged as a reliable tool to screen solvents based on a variety of fluid mixture properties. In this study, we screened ILs for the extraction of lactic acid as a model drug using COSMO-RS. Six cations and 20 anions were selected and combined to form 120 ILs, which were then assessed for recovery of lactic acid. The activity coefficient at infinite dilution, capacity, selectivity, performance index, and solvation energy values for all of the combinations were predicted, by which the effectiveness of each IL was evaluated. ILs without aromatic rings showed greater efficiencies than ILs containing aromatic rings. Moreover, the sulphate anion-cation combinations showed the highest capacities and selectivities. Overall, tetramethylammonium sulfate was found to be the best extractant for lactic acid. The COSMO-RS predictions were validated with experimental data, and the results showed a maximum difference of ~8.0 between the predicted and experimental values.

DOI： 10.1016/j.molliq.2020.113122

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Liquid marbles (LMs) have recently shown a great promise as microbioreactors to construct self-supported aqueous compartments for chemical and biological reactions. However, the evaporation of the inner aqueous liquid core has limited their application, especially in studying cellular functions. Hydrogels are promising scaffolds that provide a spatial environment suitable for three-dimensional cell culture. Here, we describe the fabrication of redox-responsive hydrogel marbles (HMs) as a three-dimensional cell culture platform. The HMs are prepared by introducing an aqueous mixture of a tetra-thiolated polyethylene glycol (PEG) derivative, thiolated gelatin (Gela-SH), horseradish peroxidase, a small phenolic compound, and human hepatocellular carcinoma cells (HepG2) to the inner aqueous phase of LMs. Eventually, HepG2 cells are encapsulated in the HMs then immersed in culture media, where they proliferate and form cellular spheroids. Experimental results show that the Gela-SH concentration strongly influences the physicochemical and microstructure properties of the HMs. After 6 days in culture, the spheroids were recovered from the HMs by degrading the scaffold, and examination showed that they had reached up to about 180 μm in diameter depending on the Gela-SH concentration, compared with 60 μm in conventional HMs without Gela-SH. After long-term culture (over 12 days), the liver-specific functions (secretion of albumin and urea) and DNA contents of the spheroids cultured in the HMs were elevated compared with those cultured in LMs. These results suggest that the developed HMs can be useful in designing a variety of microbioreactors for tissue engineering applications.

DOI： 10.1016/j.jbiosc.2020.05.010

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Assembling proteins in close vicinity to each other provides an opportunity to gain unique function because collaborative and even synergistic functionalities can be expected in an assembled form. There have been a variety of strategies to synthesize functional protein assemblies but site-specific covalent assembly of monomeric protein units without impairing their intrinsic function remains challenging. Herein we report a powerful strategy to design protein assemblies by using microbial transglutaminase (MTG). A serendipitous discovery of self-crosslinking of enhanced green fluorescent protein (EGFP) fused with StrepTag I at the C-terminus revealed that EGFP was assembled through the crosslinking of the Lys (K) residue in the C-terminus of EGFP and the Gln (Q) residue in StrepTag I (AWRHPQFGG). Site-directed mutagenesis of the residues next to the K and Q yielded EGFP assemblies with higher molecular weights. An optimized peptide tag comprised of both K and Q residues (HKRWRHYQRGG) enabled the assembly of different types of proteins of interest (POI) when it was fused to either the N- or C-terminus. The peptide tag that enabled the self-polymerization of the functional POI without a scaffold was designated as a 'PolyTag'.

DOI： 10.1016/j.ab.2020.113700

記述言語：その他   掲載種別：研究論文（学術雑誌）  

DOI： 10.3390/cosmetics7030052

記述言語：英語   掲載種別：研究論文（学術雑誌）  

その他リンク： https://doi.org/10.1039/C9TA13077B

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Efficient and selective transport of rhodium(III) across a polymer inclusion membrane (PIM) from a 0.1 mol dm(-3) HCl feed solution, also containing iron(III), to a receiving solution containing 0.1 mol dm(-3) HCl and 4.9 mol dm(-3) NH4Cl was achieved using a phosphonium-type ionic liquid, trioctyl(dodecyl)phosphonium chloride (P88812Cl), as the metal ion carrier. The optimum PIM composition for the Rh(III) transport was 50 wt % poly(vinylidene-co-hexafluoropropylene) (PVDF-HFP), 30 wt % P88812Cl, and 20 wt % plasticizer 2-nitrophenyl octyl ether (2NPOE). The driving force for the Rh(III) transport was suggested to be the concentration difference of the chloride ion between the feed and the receiving solutions. More than 70% rhodium(III) could be recovered from the receiving solution, and no transport of iron(III) was observed; however, the two metal ions cannot be separated by liquid-liquid extraction. This is the first report of selective transport of rhodium(III) across a polymer inclusion membrane.

DOI： 10.1021/acsomega.0c00867

記述言語：その他   掲載種別：研究論文（学術雑誌）