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DOI： 10.1039/C8CC08163H

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DOI： 10.1021/acs.molpharmaceut.7b00894

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Language：English   Publishing type：Research paper (scientific journal)  

Publisher：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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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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Language：English   Publisher：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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Publisher：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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Publisher：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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Language：English   Publisher：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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DOI： 10.1039/d3cc06130b

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Ionic liquid (IL)-based transdermal formulations have gained significant attention because of their high skin penetration efficiency and ease of design. However, many IL-based formulations exhibit low viscosity, which hinders direct administration and leads to less efficient drug delivery. Therefore, there is a pressing need for specialized formulations with improved viscosity and efficacy as a drug delivery platform. In this study, we report a ready-to-use transdermal patch system utilizing IL-in-oil (IL/O) microemulsions to deliver acyclovir, a sparingly soluble antiviral drug. To prepare the patch system, a mixture containing equal weights of IL/O microemulsions and adhesive (Durotak 87–4098) was homogenized, subsequently coated on a liner, and covered by a support film. These patches were produced with varying thicknesses (100 μm, 200 μm, 300 μm, and 500 μm) via a solvent evaporation technique. A 24-hour in vitro skin permeation study revealed that the thinnest patch (100 μm) delivered more than 45 % of the loaded drug. Drug delivery rate gradually reduced as the patch thickness increased, accounting for 22 % and 14 % drug permeation by 200 μm and 300 μm patches respectively. A 30-day stability study at room temperature demonstrated that neither the physical appearance nor the active ingredient content changed, validating the physical and chemical stability of the patches. Skin permeation mechanism by Fourier transform infrared spectroscopic analysis of the skin suggested that the IL/O patch possesses the capability to modify the lipid barrier in the stratum corneum thus facilitating drug diffusion. In vitro skin irritation studies on reconstructed human epidermal tissue and Yucatan micropig skin revealed that the patch exhibits no skin irritation. We believe that the adhesive nature of this newly developed IL-based patch holds significant promise as a transdermal drug delivery platform.

DOI： 10.1016/j.molliq.2024.124184

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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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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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Ulva lactuca, a green seaweed that is widely distributed in Indonesia, is abundant but still underutilized. Even though this seaweed contains a sulfated polysaccharide called ulvan as much as 30-40% of its dry biomass and secondary metabolite. These components can be applied in various fields including as a reducing agent for silver ions in the bottom up synthesis of silver nanoparticles. The utilization of seaweed extract combined with ultrasonication is expected to enhance the efficacy of environmentally friendly silver nanoparticle synthesis. The objective of this study was to obtain the crude extract of U. lactuca and to investigate the impact of extract concentration and ultrasonication duration on the synthesis of silver nanoparticles. The study consists of two main phases: bio-synthesis employing different concentrations of the U. lactuca crude extract and bio-synthesis using selected extract concentrations combined with ultrasonic assistance for varying durations. The results of this study indicate that the crude extract of U. lactuca is a crude ulvan polysaccharide with a yield value and sulfate content of 26.9 ± 0.90% and 20.04 ± 1.02%, respectively. A reddish-brown color indicates the formation of silver nanoparticles. Based on the absorbance intensity, a 10% (v/v) concentration of ulvan crude extract produced the highest absorbance intensity (0.038 a.u). In addition, the ultrasonication duration of 60 minutes has succeeded in producing the smallest particle size (267.40 ± 6.52 nm) with a homogeneous particle distribution (PdI 0.265 ± 0.05). Scanning electron microscope (SEM) images depicted oval-shaped silver nanoparticles, while the Fourier-transform infrared (FTIR) spectrum indicated the degradation of sulfate and polysulfide functional groups in the crude extract during the synthesis process. These findings highlight the significant role of sulfate/sulfide groups present in the U. lactuca crude extract in the synthesis of silver nanoparticles.

DOI： 10.15578/squalen.802

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DOI： 10.1021/acsami.3c03900

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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

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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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Language：Others   Publishing type：Research paper (scientific journal)   Publisher：American Chemical Society (ACS)  

DOI： 10.1021/acsomega.2c06654

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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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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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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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Language：Others   Publishing type：Research paper (scientific journal)   Publisher：AMER CHEMICAL SOC  

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 beta-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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Transdermal drug delivery systems (TDDSs) may be useful for preventing various diseases including cancer. However, the stratum corneum (SC) inhibits the permeation of foreign particles into the skin. To obtain an effective TDDS, we developed a protein-containing nanocarrier (PCNC) comprising an antigenic protein (ovalbumin/OVA) stabilized by a combination of surfactants, i.e., a lipid-based surface-active ionic liquid and Tween-80. The PCNC was lyophilized to remove water and cyclohexane and then dispersed in isopropyl myristate. It is biocompatible both in vitro and in vivo, and is suitable for use in a therapeutic TDDS. The skin permeability of the PCNC was significantly (p < 0.0001) 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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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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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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DOI： 10.1021/acsami.1c16659

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DOI： 10.1016/j.ijpharm.2021.121129

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DOI： 10.1021/acsami.1c11533

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DOI： 10.1021/acs.molpharmaceut.1c00324

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DOI： 10.1021/acsabm.1c00563

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DOI： 10.1016/j.ijpharm.2021.120582

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DOI： 10.1021/acsami.1c03111

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DOI： 10.1021/acs.bioconjchem.1c00027

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DOI： 10.1016/j.ejps.2020.105667

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DOI： 10.1038/s41598-020-63362-4

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DOI： 10.1016/j.molliq.2020.114424

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DOI： 10.1016/j.jbiosc.2020.05.010

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DOI： 10.1021/acsabm.0c00940

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DOI： 10.1039/D0CC04491A

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DOI： 10.1021/acs.molpharmaceut.0c00598

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DOI： 10.3390/COSMETICS7030052

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DOI： 10.1021/acssuschemeng.0c03419

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DOI： 10.1016/j.ab.2020.113700

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DOI： 10.1016/j.ijpharm.2020.119335

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DOI： 10.3390/pharmaceutics12040392

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DOI： 10.1021/acssuschemeng.9b07773

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DOI： 10.1248/bpb.b19-00642

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DOI： 10.1021/acsomega.9b04163

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.molliq.2019.112166

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1021/acs.molpharmaceut.9b01104

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.ijpharm.2019.118777

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.3390/pharmaceutics11110563

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.jcis.2019.04.095

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.ijpharm.2019.118495

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.ijpharm.2019.05.020

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1021/acsabm.9b00275

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.molliq.2019.01.063

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1021/acs.langmuir.8b02809

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.jphotochem.2018.10.006

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1039/c9cc02812a

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1002/chem.201900370

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1252/jcej.18we060

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1002/biot.201800085

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1021/acsabm.8b00271

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.ijpharm.2018.05.021

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.jconrel.2012.03.021

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1111/j.1872-034X.2011.00868.x

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.canlet.2011.02.042

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1002/ejoc.201001656

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1021/ja063040x

Event date： 2023.3

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：東京理科大学   Country：Japan  

Event date： 2023.3

Language：English   Presentation type：Oral presentation (general)  

Country：Japan  

Event date： 2022.11

Language：English   Presentation type：Oral presentation (general)  

Country：Japan  

Event date： 2022.11

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：東京大学   Country：Japan  

Event date： 2022.10

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：オンライン   Country：Japan  

Event date： 2022.10

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：東京工業大学   Country：Japan  

Event date： 2022.10

Language：English  

Country：Indonesia  

Event date： 2022.9

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：名古屋大学   Country：Japan  

Event date： 2022.8

Language：English   Presentation type：Oral presentation (general)  

Country：Malaysia  

Event date： 2022.7

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：鳥取大学/オンライン   Country：Japan  

Event date： 2022.7

Language：English   Presentation type：Oral presentation (general)  

Country：Indonesia  

Event date： 2022.7

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：崇城大学   Country：Japan  

Event date： 2022.3

Language：Japanese   Presentation type：Oral presentation (general)  

Country：Japan  

Event date： 2022.3

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：オンライン   Country：Japan  

Event date： 2022.3

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：オンライン   Country：Japan  

Event date： 2021.12

Language：Japanese   Presentation type：Oral presentation (general)  

Country：Japan  

Event date： 2021.9

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：オンライン   Country：Japan  

Event date： 2021.9

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：オンライン   Country：Japan  

Event date： 2021.5

Language：Japanese  

Venue：オンライン   Country：Japan  

Event date： 2021.3

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：オンライン   Country：Japan  

Event date： 2019.11

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：オンライン   Country：Japan  

Event date： 2019.10

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：オンライン   Country：Japan  

Event date： 2019.9

Language：English  

Country：Japan  

Event date： 2019.9

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：オンライン   Country：Japan  

Event date： 2019.9

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：東北大学   Country：Japan  

Event date： 2019.7

Language：Japanese  

Venue：セミナーハウス（東京都八王子市）   Country：Japan  

Event date： 2019.7 - 2018.7

Language：English  

Country：Taiwan, Province of China  

Event date： 2019.3

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：甲南大学   Country：Japan  

Event date： 2018.12

Language：English   Presentation type：Oral presentation (general)  

Country：Japan  

Event date： 2018.12

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：東京大学   Country：Japan  

Event date： 2018.11

Language：English  

Country：Taiwan, Province of China  

Event date： 2018.10

Language：English   Presentation type：Oral presentation (general)  

Country：Korea, Republic of  

Event date： 2018.9

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：大阪大学   Country：Japan  

Event date： 2018.7

Language：Japanese  

Venue：ANAホリデイ・イン リゾート宮崎   Country：Japan  

Event date： 2018.6

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：長崎ブリックホール   Country：Japan  

Event date： 2018.3

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：日本大学   Country：Japan  

Event date： 2017.12

Language：English  

Country：Japan  

Event date： 2017.10

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：志賀島休暇村   Country：Japan  

Event date： 2017.9

Language：Japanese  

Venue：東京大学   Country：Japan  

Event date： 2017.7

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：みやこめっせ   Country：Japan  

Event date： 2017.7

Language：Japanese  

Venue：東京国際フォーラム   Country：Japan  

Event date： 2017.5

Language：Japanese  

Venue：幕張メッセ   Country：Japan  

Language：Others  

Country：Other  

Event date： 2024.3

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：つくば  

Event date： 2024.3

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：日本大学船橋キャンパス  

Event date： 2024.3

Language：English   Presentation type：Oral presentation (general)  

Event date： 2024.3

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：大阪公立大学  

Event date： 2024.3

Language：English   Presentation type：Oral presentation (general)  

Event date： 2024.3

Language：English   Presentation type：Oral presentation (general)  

Event date： 2024.3

Language：English   Presentation type：Oral presentation (general)  

Event date： 2024.3

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：大阪公立大学  

Event date： 2024.3

Language：Japanese  

Venue：大阪公立大学 中百舌鳥キャンパス  

Event date： 2024.3

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：オンライン  

Event date： 2024.3

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：オンライン  

Event date： 2024.3

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：オンライン  

Event date： 2023.12

Language：English   Presentation type：Oral presentation (general)  

Country：Indonesia  

Event date： 2023.12

Language：English   Presentation type：Oral presentation (general)  

Country：Korea, Republic of  

Event date： 2023.12

Language：English   Presentation type：Oral presentation (general)  

Country：Korea, Republic of  

Event date： 2023.12

Language：English   Presentation type：Oral presentation (general)  

Country：Korea, Republic of  

Event date： 2023.12

Language：English   Presentation type：Oral presentation (general)  

Country：Korea, Republic of  

Event date： 2023.12

Language：English   Presentation type：Oral presentation (general)  

Country：Korea, Republic of  

Event date： 2023.12

Language：English   Presentation type：Oral presentation (general)  

Country：Korea, Republic of  

Event date： 2023.12

Language：English   Presentation type：Oral presentation (general)  

Country：Korea, Republic of  

Event date： 2023.12

Language：English   Presentation type：Oral presentation (general)  

Country：Korea, Republic of  

Event date： 2023.12

Language：English   Presentation type：Oral presentation (general)  

Country：Korea, Republic of  

Event date： 2023.11

Language：Japanese  

Venue：早稲田大学先進研究センター  

Event date： 2023.11

Language：Japanese  

Venue：早稲田大学リサーチイノベーションセンター  

Event date： 2023.11

Language：Japanese  

Venue：早稲田大学リサーチイノベーションセンター  

Event date： 2023.11

Language：Japanese  

Venue：早稲田大学リサーチイノベーションセンター（121号館）B1F  

Event date： 2023.11

Language：English  

Country：Korea, Republic of  

Event date： 2023.11

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：熊本大学  

Event date： 2023.10

Language：Japanese  

Venue：タワーホール船堀  

Event date： 2023.10

Language：Japanese  

Venue：タワーホール船堀  

Event date： 2023.10

Language：English  

Country：Viet Nam  

Event date： 2023.10

Language：English  

Country：Viet Nam  

Event date： 2023.9

Language：Japanese  

Venue：東京大学  

Event date： 2023.9

Language：Japanese  

Venue：大阪公立大学 I-siteなんば  

Event date： 2023.9

Language：Japanese  

Venue：高野山大学  

Event date： 2023.9

Language：Japanese  

Venue：高野山大学  

Event date： 2023.9

Language：Japanese  

Venue：福岡大学  

Event date： 2023.9

Language：Japanese  

Venue：福岡大学七隈キャンパス  

Event date： 2023.9

Language：Japanese  

Venue：福岡大学 七隈キャンパス  

Event date： 2023.9

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：福岡大学  

Event date： 2023.9

Language：Japanese  

Venue：福岡大学 七隈キャンパス  

Event date： 2023.9

Language：Japanese  

Venue：福岡大学  

Event date： 2023.9

Language：Japanese  

Venue：東京理科大学野田キャンパス薬学部  

Event date： 2023.9

Language：Japanese  

Venue：千葉  

Event date： 2023.9

Language：Japanese  

Venue：東京理科大学野田キャンパス薬学部  

Event date： 2023.9

Language：Japanese  

Venue：東京理科大学野田キャンパス薬学部  

Event date： 2023.9

Language：Japanese  

Venue：東京理科大学  

Event date： 2023.9

Language：Japanese  

Venue：東京大学  

Event date： 2023.9

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：名古屋大学  

Event date： 2023.8 - 2023.10

Language：Japanese  

Venue：東京理科大学野田キャンパス薬学部  

Event date： 2023.7

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：幕張メッセ　国際会議場  

Event date： 2023.7

Language：Japanese  

Venue：幕張メッセ国際会議場  

Event date： 2023.7

Language：Japanese  

Venue：幕張メッセ　国際会議場  

Event date： 2023.7

Language：Japanese  

Venue：あいち健康の森プラザホテル  

Event date： 2023.7

Language：Japanese  

Venue：あいち健康の森プラザホテル  

Event date： 2023.7

Language：Japanese  

Venue：あいち健康の森プラザホテル  

Event date： 2023.7

Language：Japanese  

Venue：鹿児島大学  

Event date： 2023.7

Language：Japanese  

Venue：鹿児島大学  

Event date： 2023.7

Language：English  

Country：Taiwan, Province of China  

Event date： 2023.7

Language：English  

Country：Taiwan, Province of China  

Event date： 2023.7

Language：Japanese  

Venue：北九州  

Event date： 2023.7

Language：Japanese  

Venue：北九州国際会議場  

Event date： 2023.6

Language：Japanese  

Venue：砺波青少年自然の家  

Event date： 2023.3

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：東京理科大学   Country：Japan  

Event date： 2023.3

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：東京理科大学   Country：Japan  

Event date： 2022.12

Language：English  

Country：Indonesia  

Event date： 2022.11

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：鹿児島大学   Country：Japan  

Event date： 2022.11

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：鹿児島大学   Country：Japan  

Event date： 2022.10

Language：English   Presentation type：Oral presentation (general)  

Country：Indonesia  

Event date： 2022.9

Language：Japanese  

Venue：信州大学   Country：Japan  

Event date： 2022.9

Language：Japanese  

Venue：名古屋大学   Country：Japan  

Event date： 2022.9

Language：Japanese  

Venue：名古屋大学   Country：Japan  

Event date： 2022.9

Language：Japanese  

Venue：名古屋大学   Country：Japan  

Event date： 2022.8

Language：English   Presentation type：Oral presentation (general)  

Country：Malaysia  

Event date： 2022.8

Language：English   Presentation type：Oral presentation (general)  

Country：Japan  

Event date： 2022.8

Language：English   Presentation type：Oral presentation (general)  

Country：Japan  

Event date： 2022.7

Language：Japanese  

Venue：福岡大学   Country：Japan  

Event date： 2022.7

Language：Japanese  

Venue：北九州国際会議場   Country：Japan  

Event date： 2022.6

Language：Japanese  

Venue：オンライン   Country：Japan  

Event date： 2022.6

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：オンライン   Country：Japan  

Event date： 2022.3

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：オンライン   Country：Japan  

Event date： 2022.3

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：オンライン   Country：Japan  

Event date： 2022.3

Language：Japanese  

Venue：オンライン   Country：Japan  

Event date： 2022.3

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：オンライン   Country：Japan  

Event date： 2021.12

Language：Japanese  

Country：Japan  

Event date： 2021.12

Language：Japanese  

Country：Japan  

Event date： 2021.12

Language：Japanese  

Venue：オンライン   Country：Japan  

Event date： 2021.11

Language：Japanese  

Venue：オンライン   Country：Japan  

Event date： 2021.9

Language：Japanese  

Venue：オンライン   Country：Japan  

Event date： 2021.9

Language：Japanese  

Venue：オンライン   Country：Japan  

Event date： 2021.7

Language：Japanese  

Venue：オンライン   Country：Japan  

Event date： 2021.7

Language：Japanese  

Venue：オンライン   Country：Japan  

Event date： 2021.7

Language：Japanese  

Venue：オンライン   Country：Japan  

Event date： 2021.6

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：幕張メッセ国際会議場   Country：Japan  

Event date： 2021.3

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：オンライン   Country：Japan  

Event date： 2021.3

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：オンライン   Country：Japan  

Event date： 2021.3

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：オンライン   Country：Japan  

Event date： 2020.3 - 2019.3

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：東京理科大学   Country：Japan  

Event date： 2020.3 - 2019.3

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：東京理科大学   Country：Japan  

Event date： 2020.3 - 2019.3

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：東京理科大学   Country：Japan  

Event date： 2020.3 - 2019.3

Language：Japanese  

Venue：関西大学   Country：Japan  

Event date： 2020.3 - 2019.3

Language：Japanese  

Venue：岡山大学   Country：Japan  

Event date： 2019.12

Language：English   Presentation type：Oral presentation (general)  

Country：Korea, Republic of  

Event date： 2019.12

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：オンライン   Country：Japan  

Event date： 2019.11

Language：Japanese  

Venue：オンライン   Country：Japan  

Event date： 2019.11

Language：English  

Country：Japan  

Event date： 2019.9

Language：Japanese  

Venue：オンライン   Country：Japan  

Event date： 2019.9

Language：Japanese  

Venue：オンライン   Country：Japan  

Event date： 2019.9

Language：Japanese  

Venue：オンライン   Country：Japan  

Event date： 2019.9

Language：Japanese  

Venue：オンライン   Country：Japan  

Event date： 2019.9

Language：Japanese  

Venue：東北大学   Country：Japan  

Event date： 2019.9

Language：Japanese  

Venue：東北大学   Country：Japan  

Event date： 2019.7

Language：Japanese  

Venue：琵琶湖国定公園白浜荘   Country：Japan  

Event date： 2019.7

Language：Japanese  

Venue：セミナーハウス（東京都八王子市）   Country：Japan  

Event date： 2019.3

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：甲南大学   Country：Japan  

Event date： 2019.3

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：甲南大学   Country：Japan  

Event date： 2018.12

Language：Japanese  

Country：Japan  

Event date： 2018.12

Language：English  

Country：Thailand  

Event date： 2018.12

Language：English   Presentation type：Oral presentation (general)  

Country：Thailand  

Event date： 2018.3 - 2019.3

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：京都大学   Country：Japan  

Event date： 2018.3

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：広島大学   Country：Japan  

Event date： 2017.12

Language：English  

Country：Korea, Republic of  

Event date： 2017.9

Language：Japanese  

Venue：東京大学   Country：Japan  

Event date： 2017.8

Language：English   Presentation type：Oral presentation (general)  

Country：China  

Language：English  

DOI： 10.3390/pharmaceutics12030240

Language：Japanese  

Type：Peer review 

Number of peer-reviewed articles in foreign language journals：14

Number of peer-reviewed articles in Japanese journals：0

Proceedings of International Conference Number of peer-reviewed papers：0

Proceedings of domestic conference Number of peer-reviewed papers：0

Type：Competition, symposium, etc. 

Type：Competition, symposium, etc. 

Type：Peer review 

Number of peer-reviewed articles in foreign language journals：15

Number of peer-reviewed articles in Japanese journals：0

Proceedings of International Conference Number of peer-reviewed papers：0

Proceedings of domestic conference Number of peer-reviewed papers：0

Type：Competition, symposium, etc. 

Type：Competition, symposium, etc. 

Type：Competition, symposium, etc. 

Type：Peer review 

Number of peer-reviewed articles in foreign language journals：8

Number of peer-reviewed articles in Japanese journals：0

Proceedings of International Conference Number of peer-reviewed papers：0

Proceedings of domestic conference Number of peer-reviewed papers：0

Type：Competition, symposium, etc. 

Type：Competition, symposium, etc. 

Type：Competition, symposium, etc. 

Type：Competition, symposium, etc. 

Type：Peer review 

Number of peer-reviewed articles in foreign language journals：13

Number of peer-reviewed articles in Japanese journals：0

Proceedings of International Conference Number of peer-reviewed papers：0

Proceedings of domestic conference Number of peer-reviewed papers：0

Type：Competition, symposium, etc. 

Type：Competition, symposium, etc. 

Type：Competition, symposium, etc. 

Type：Competition, symposium, etc. 

Type：Competition, symposium, etc. 

Type：Peer review 

Number of peer-reviewed articles in foreign language journals：10

Number of peer-reviewed articles in Japanese journals：0

Proceedings of International Conference Number of peer-reviewed papers：0

Proceedings of domestic conference Number of peer-reviewed papers：0

Type：Competition, symposium, etc. 

Type：Competition, symposium, etc. 

Type：Competition, symposium, etc. 

Type：Competition, symposium, etc. 

Number of participants：135

Type：Competition, symposium, etc. 

Type：Competition, symposium, etc. 

Type：Competition, symposium, etc. 

Type：Competition, symposium, etc. 

Type：Peer review 

Number of peer-reviewed articles in foreign language journals：8

Number of peer-reviewed articles in Japanese journals：0

Proceedings of International Conference Number of peer-reviewed papers：0

Proceedings of domestic conference Number of peer-reviewed papers：0

Type：Competition, symposium, etc. 

Type：Competition, symposium, etc. 

Type：Competition, symposium, etc. 

Type：Competition, symposium, etc. 

Type：Peer review 

Number of peer-reviewed articles in foreign language journals：3

Number of peer-reviewed articles in Japanese journals：0

Proceedings of International Conference Number of peer-reviewed papers：0

Proceedings of domestic conference Number of peer-reviewed papers：0

Type：Competition, symposium, etc. 

Type：Competition, symposium, etc. 

Number of participants：450

Type：Competition, symposium, etc. 

Number of participants：106

Audience： General,　Scientific,　Company,　Civic organization,　Governmental agency

Type：Other