Utility of the Three-dimensional Cultured Human Skin Model as a Tool to Evaluate Skin Permeation of Drugs
Tetsuya Watanabe1, Tetsuya Hasegawa1, Hidekazu Takahashi2, Takuya Ishibashi2, Kozo Takayama3 and Kenji Sugibayashi1
1 Josai University, 2 Toyobo Co., Ltd., 3 Hoshi University
Correspondence: Kenji Sugibayashi, Ph.D.
Faculty of Pharmaceutical Sciences, Josai University
1-1 Keyakidai, Sakado, Saitama 350-0295, Japan. Tel: 0492-71-7943, Fax: 0492-71-7943, E-mail: sugib@josai.ac.jp

Original paper :AATEX 8(1):1-14
Abstract
Three-dimensional cultured human skin model (cultured human skin) was evaluated for prediction of skin permeability of drugs. The permeation data of different drugs from their aqueous solution in the cultured human skin were compared with those through excised human and rat skin. Although the cumulative amount of each drug that permeated through the cultured human skin was about 10-fold higher than those through the excised human and hairless rat skin, a good correlation was found between the cultured human skin and excised skin permeabilities. In addition, time profiles for skin permeation of each drug were very analogical for both the skin membranes. This was probably due to similar partition parameters of the drugs from aqueous solution to both skin preparations, although the diffusion parameters in skin barrier were markedly different among the membranes. The rate-limiting layer for cultured human skin permeation was evaluated using isosorbide-5-mononitrate (ISMN) and isosorbide-dinitrate (ISDN). The resistances of stratum corneum in the cultured human skin and excised hairless rat skin were 74.8 and 95.4 % of the total resistance for ISMN permeation, and 66.1 and 94.7 % for ISDN permeation. Those of the total epidermis in the cultured human skin were 99.4 and 93.5 % for ISMN and ISDN permeation, respectively. It is clear from these results that the total epidermis is the primary barrier in the cultured human skin, whereas the stratum corneum alone is the barrier in excised hairless rat skin. These results suggested that one has to use this cultured human skin model under consideration of different barrier properties of the model from those of excised hairless rat and human skin when predicting skin permeation of drugs.

Keywords: three-dimensional cultured human skin model, skin permeation, high through-put screening, alternative skin


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