Utility of Three-Dimensional Skin From Human-Induced Pluripotent Stem Cells as a Tool to Evaluate Transdermal Drug Permeation |
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| Affiliation: | 1. Department of Biopharmaceutics, Kyoto Pharmaceutical University, Yamashina-ku, Kyoto 607-8414, Japan;2. Laboratory of Stem Cell Regulation, National Institutes of Biomedical Innovation, Health and Nutrition, Ibaraki, Osaka 567-0085, Japan;3. Department of Pharmaceutical Technology, Kobe Pharmaceutical University, Higashinada-ku, Kobe 658-8558, Japan;1. Faculty of Pharmaceutical Sciences, Sojo University, Ikeda 4-22-1, Nishi-ku, Kumamoto 860-0082, Japan;2. Graduate School of Pharmaceutical Sciences, Kumamoto University, Oe-honmachi 5-1, Chuo-ku, Kumamoto 862-0082, Japan;3. DDS Research Institute, Sojo University, Ikeda 4-22-1, Nishi-ku, Kumamoto 860-0082, Japan;1. Department of Biochemical and Chemical Engineering, Laboratory of Solids Process Engineering, Technical University Dortmund, Emil-Figge-Str. 68, Dortmund 44227, Germany;2. Department of Pharmaceutical Technologies, Merck Healthcare KGaA, Frankfurter Str. 250, Darmstadt 64293, Germany;1. Therapeutics & Biotechnology Division, Korea Research Institute of Chemical Technology, 141 Gajeong-ro, Yuseong-gu, Daejeon 34114, Republic of Korea;2. Division of Chemical and Medical Metrology, Center for Bioanalysis, Korea Research Institute of Standards and Science, Daejeon 34113, Republic of Korea;1. Institute of Condensed Matter and Nanosciences, UCLouvain, 1 Place Louis Pasteur, B-1348 Louvain-la-Neuve, Belgium;2. Unité de Chimie Biologique et Structurale, Chemistry Department, UNamur, 61 rue de Bruxelles, B-5000 Namur, Belgium |
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| Abstract: | Transdermal drug delivery is an attractive route for administration of drugs, and it offers several advantages such as painless administration. To accurately predict the rate of human skin permeation for new transdermal drug formulations, we developed a novel assessment system using induced pluripotent stem cells (iPSCs). Skin was generated from iPSC-derived keratinocytes and fibroblasts. In the histological and immunohistochemical examination, cellular markers (keratin 14 and keratin 10) for the epidermal basal and suprabasal layers were clearly detected within the multilayer structures produced in the human iPSC-based three-dimensional skin model. The results from our permeation study indicate that an initial lag time exists during permeation of 5(6)-carboxyfluorescein and fluorescein isothiocyanate dextran 4000. Furthermore, the permeation for these model drugs in human iPSC-based skin was inversely proportional to the molecular weight of the drugs. These results of the present iPSC-based skin are useful basic information as a first step for developing a new assessment system to predict the efficacy of drug permeation in human skin by using iPSC-based skin. |
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| Keywords: | transdermal skin drug delivery system(s) absorption |
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