Miki Ryotaro, Ichitsuka Yasuna, Yamada Takumi, Kimura Soichiro, Egawa Yuya, Seki Toshinobu, Juni Kazuhiko, Ueda Hideo, Morimoto Yasunori
Faculty of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama 350-0295, Japan.
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.
Eur J Pharm Sci. 2015 Jan 23;66:41-9. doi: 10.1016/j.ejps.2014.09.024. Epub 2014 Oct 12.
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.
我们旨在开发一种高通量筛选（HTS）系统，通过使用一种能够模拟亲脂性和亲水性化合物在人体皮肤渗透行为的人工膜，对人体皮肤通透性进行初步预测。在本研究中，我们合成了一种含有聚二甲基硅氧烷（PDMS）和聚乙二醇（PEG）6000的共聚物，并将其浸渍到支撑膜过滤器上，以制备PDMS/PEG 6000共聚物浸渍膜。此外，我们合成了另一种不含PEG单元的聚合物，并用它制备了一种浸渍膜，以确定PEG 6000单元在PDMS/PEG 6000共聚物浸渍膜中的作用。通过使用双室扩散池，基于12种不同亲脂性模型化合物的渗透系数，评估了浸渍膜的渗透特性，并将这些渗透系数与人体皮肤的渗透系数进行了比较。我们发现PDMS/PEG 6000共聚物浸渍膜与人体皮肤的渗透系数之间具有良好的相关性。此外，我们使用6种模型化合物评估了PDMS/PEG 6000共聚物96孔板模型的渗透特性。我们发现使用96孔板的PDMS/PEG 6000共聚物与人体皮肤的渗透系数之间具有理想的相关性。因此，PDMS/PEG 6000共聚物将是初步评估亲脂性和亲水性化合物在人体皮肤通透性的良好候选材料。
