Matsuzaki K, Imaoka T, Asano M, Miyajima K
Faculty of Pharmaceutical Sciences, Kyoto University, Japan.
Chem Pharm Bull (Tokyo). 1993 Mar;41(3):575-9. doi: 10.1248/cpb.41.575.
Several model membrane systems have been reported to predict the skin permeability of drugs, but model membranes using stratum corneum (SC) lipids have never been reported. Thus, we developed a model membrane system for drug permeation study by fixing liposomes composed of SC lipids (ceramides, palmitic acid, cholesterol, and cholesterol-3-sulfate) onto a supporting filter, Biodyne B. The permeability of several drugs with different lipophilicities was investigated. Permeability increased with drug lipophilicity, estimated from the octanol/buffer solubility ratio of the drug. For relatively polar drugs, however, the permeability was almost constant, and very close to the value of a K+ ion, suggesting the membrane has both lipidic and aqueous pathways. Drug permeability through our system was compared with that through guinea pig skin. A good correlation (r = 0.880) was observed, although the former was one order of magnitude greater than the latter. Our model system will be useful not only for practical application, but also for basic studies, such as the elucidation of the relationships between SC lipid composition and drug permeability.
已有报道称几种模型膜系统可用于预测药物的皮肤渗透性，但使用角质层（SC）脂质的模型膜尚未见报道。因此，我们通过将由SC脂质（神经酰胺、棕榈酸、胆固醇和胆固醇-3-硫酸盐）组成的脂质体固定在支持性滤膜Biodyne B上，开发了一种用于药物渗透研究的模型膜系统。研究了几种具有不同亲脂性的药物的渗透性。渗透性随药物亲脂性增加，药物亲脂性由药物的正辛醇/缓冲液溶解度比估算得出。然而，对于相对极性较强的药物，渗透性几乎恒定，且非常接近钾离子的渗透性值，这表明该膜同时具有脂质通道和水性通道。将我们系统中药物的渗透性与通过豚鼠皮肤的渗透性进行了比较。尽管前者比后者大一个数量级，但仍观察到良好的相关性（r = 0.880）。我们的模型系统不仅将用于实际应用，还将用于基础研究，例如阐明SC脂质组成与药物渗透性之间的关系。
