基于计算机模拟的经皮给药研究中角质层脂质模型搭建及其稳定性考察

Modeling stratum corneum lipids and examining its stability for studying on transdermal drug delivery by computer simulations

经皮给药系统成为近年来药物制剂开发研究的热点,皮肤角质层脂质的屏障功能是限制其开发应用的最大因素。本文采用计算机模拟技术成功搭建了角质层脂质模型,并对其稳定性进行了考察。结果表明,组成比为神经酰胺:胆固醇:游离脂肪酸=2:2:1的模型不仅能够合理地解释皮肤角质层的屏障特性,并具备应对水合程度、离子强度和pH变化的很好的稳定性。研究结果为深入阐明经皮给药系统与胞间脂质层的相互作用奠定了基础,对于经皮给药系统的研发具有一定的意义。

Nowadays, transdermal drug delivery has become a focus in pharmaceutical preparations. However, the barrier function of stratum corneum lipids limits its potential applications and development to a large extent, corneum is of central importance. In this work, we have successfully modeled stratum corneum lipids and examined its stability by computer simulations. Results show that the model whose composition is 2：2：l（ceramide：cholesterol：free fatty acid） can reasonably explain the barrier property of intercellular lipids, and it can keep stable structure with the degree of hydration, ionic strength and pH changes. Our works lay a foundation for further research of the interaction between transdermal drug delivery system and the intercellular lipid layer, and have a certain significance for studying on transdermal drug delivery.