Department of Pharmaceutical Chemistry, Semmelweis University, 9 Hőgyes Endre Street, 1092 Budapest, Hungary.
Eur J Pharm Sci. 2012 Apr 11;45(5):698-707. doi: 10.1016/j.ejps.2012.01.011. Epub 2012 Feb 2.
The goal of this study was to develop a quick, reliable, and cost-effective permeability model for predicting transdermal penetration of compounds. The Parallel Artificial Membrane Permeability Assay (PAMPA) was chosen for this purpose, as it already has been successfully used for estimating passive gastrointestinal absorption and blood-brain barrier permeability. To match the permeability of the rate-limiting barrier in human skin, synthetic certramides, which are analogs of the ceramides present in the stratum corneum, were selected for the skin-PAMPA model. The final skin-PAMPA membrane lipid mixture (certramide, free fatty acid, and cholesterol) was selected and optimized based on data from three different human skin databases and the final model was found to correlate well to all of the databases. The reproducibility of the skin-PAMPA model was investigated and compared to that of other PAMPA models. The homogeneity of the filter-impregnated lipid mixture membrane was confirmed with Raman microscopy. It was shown that skin-PAMPA is a quick and cost-effective research tool that can serve as a useful model of skin penetration in pharmaceutical and cosmetic research.
本研究旨在开发一种快速、可靠且经济高效的渗透模型，用于预测化合物的透皮渗透。为此选择了平行人工膜渗透测定法 (PAMPA)，因为它已经成功用于估计被动胃肠道吸收和血脑屏障通透性。为了匹配人皮肤中限速屏障的通透性，选择了合成神经酰胺，它是角质层中神经酰胺的类似物，用于皮肤-PAMPA 模型。最终的皮肤-PAMPA 膜脂质混合物（神经酰胺、游离脂肪酸和胆固醇）是根据来自三个不同人体皮肤数据库的数据进行选择和优化的，最终模型与所有数据库都很好地相关。研究了皮肤-PAMPA 模型的重现性，并与其他 PAMPA 模型进行了比较。用拉曼显微镜证实了过滤浸渍脂质混合物膜的均一性。结果表明，皮肤-PAMPA 是一种快速且经济高效的研究工具，可作为药物和化妆品研究中皮肤渗透的有用模型。
