title: Development of a membrane impregnated with a poly(dimethylsiloxane)/poly(ethylene glycol) copolymer for a high-throughput screening of the permeability of drugs, cosmetics, and other chemicals across the human skin.
abstract: We aimed to develop a high-throughput screening (HTS) system for preliminary predictions of human skin permeability by using an artificial membrane that can mimic the permeation behaviour of lipophilic and hydrophilic compounds across the human skin. In this study, we synthesized a copolymer containing poly(dimethylsiloxane) (PDMS) and poly(ethylene glycol) (PEG) 6000 and impregnated it onto a supportive membrane filter to prepare a PDMS/PEG 6000 copolymer-impregnated membrane. In addition, we synthesized another polymer without PEG units and used it to prepare an impregnated membrane for determining the role of PEG 6000 units in the PDMS/PEG 6000 copolymer-impregnated membrane. The permeation characteristics of the impregnated membranes were evaluated on the basis of the permeability coefficients of 12 model compounds with different lipophilicities, by using a 2-chamber diffusion cell, and these permeability coefficients were compared with those across the human skin. We obtained a good correlation between the permeability coefficients across the PDMS/PEG 6000 copolymer-impregnated membrane and human skin. Further, we evaluated the permeation characteristics of a 96-well plate model of the PDMS/PEG 6000 copolymer by using 6 model compounds. We obtained an ideal correlation between the permeability coefficients across the PDMS/PEG 6000 copolymer using a 96-well plate and those across the human skin. Thus, the PDMS/PEG 6000 copolymer would be a good candidate for preliminary evaluation of the permeability of lipophilic and hydrophilic compounds across the human skin.
authors.affiliation: Faculty of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama 350-0295, Japan. Electronic address: rmiki@josai.ac.jp.
authors.forename: Ryotaro
authors.initials: R
authors.lastname: Miki
authors.affiliation: Faculty of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama 350-0295, Japan. Electronic address: yy09028@josai.ac.jp.
authors.forename: Yasuna
authors.initials: Y
authors.lastname: Ichitsuka
authors.affiliation: Faculty of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama 350-0295, Japan. Electronic address: syota1985jp@gmail.com.
authors.forename: Takumi
authors.initials: T
authors.lastname: Yamada
authors.affiliation: Faculty of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama 350-0295, Japan. Electronic address: sokimura@josai.ac.jp.
authors.forename: Soichiro
authors.initials: S
authors.lastname: Kimura
authors.affiliation: Faculty of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama 350-0295, Japan. Electronic address: yegawa@josai.ac.jp.
authors.forename: Yuya
authors.initials: Y
authors.lastname: Egawa
authors.affiliation: Faculty of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama 350-0295, Japan; Research Institute of TTS Technology, 1-1 Keyakidai, Sakado, Saitama 350-0295, Japan. Electronic address: sekt1042@josai.ac.jp.
authors.forename: Toshinobu
authors.initials: T
authors.lastname: Seki
authors.affiliation: Faculty of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama 350-0295, Japan. Electronic address: kjuni@josai.ac.jp.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Juni
authors.affiliation: Faculty of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama 350-0295, Japan. Electronic address: hideo@josai.ac.jp.
authors.forename: Hideo
authors.initials: H
authors.lastname: Ueda
authors.affiliation: Faculty of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama 350-0295, Japan; Research Institute of TTS Technology, 1-1 Keyakidai, Sakado, Saitama 350-0295, Japan. Electronic address: morimoto@josai.ac.jp.
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Morimoto
mesh_terms: D000287:Administration, Topical; D004129:Dimethylpolysiloxanes / Q000737:chemistry*; D004353:Drug Evaluation, Preclinical; D057166:High-Throughput Screening Assays / Q000295:instrumentation* / Q000379:methods; D006801:Humans; D008567:Membranes, Artificial; D008954:Models, Biological; D015394:Molecular Structure; D010539:Permeability; D011092:Polyethylene Glycols / Q000737:chemistry*; D012879:Skin Physiological Phenomena
chemical_list: D004129:Dimethylpolysiloxanes; D008567:Membranes, Artificial; D011092:Polyethylene Glycols; C013830:baysilon
keywords: High-throughput screening; Preliminary evaluation; Skin alternative; Skin permeability; Synthetic polymer; Transdermal delivery