MacDermaid Christopher M, Hall Kyle Wm, DeVane Russell H, Klein Michael L, Fiorin Giacomo
Institute for Computational Molecular Science and Temple Materials Institute, Philadelphia, Pennsylvania.
The Procter & Gamble Company, West Chester, Ohio.
Biophys J. 2020 Apr 7;118(7):1588-1601. doi: 10.1016/j.bpj.2020.01.044. Epub 2020 Feb 12.
The lipid matrix in the outer layer of mammalian skin, the stratum corneum, has been previously investigated by multiple biophysical techniques aimed at identifying hydrophilic and lipophilic pathways of permeation. Although consensus is developing over the microscopic structure of the lipid matrix, no molecular-resolution model describes the permeability of all chemical species simultaneously. Using molecular dynamics simulations of a model mixture of skin lipids, the self-assembly of the lipid matrix lamellae has been studied. At higher humidity, the resulting lamellar phase is maintained by partitioning excess water into isolated droplets of controlled size and spatial distribution. The droplets may fuse together to form intralamellar water channels, thereby providing a pathway for the permeation of hydrophilic species. These results reconcile competing data on the outer skin's structure and broaden the scope of molecular-based methods to improve the safety of topical products and to advance transdermal drug delivery.
哺乳动物皮肤外层角质层中的脂质基质，此前已通过多种生物物理技术进行研究，旨在确定亲水性和疏水性渗透途径。尽管关于脂质基质的微观结构已逐渐形成共识，但尚无分子分辨率模型能同时描述所有化学物质的渗透性。通过对皮肤脂质模型混合物进行分子动力学模拟，研究了脂质基质薄片的自组装过程。在较高湿度下，通过将多余的水分分配到尺寸和空间分布可控的孤立液滴中，可维持所得的层状相。这些液滴可能融合在一起形成层内水通道，从而为亲水性物质的渗透提供一条途径。这些结果协调了关于皮肤外层结构的相互矛盾的数据，并拓宽了基于分子的方法的范围，以提高局部用产品的安全性并推进透皮给药。
