Kessner D, Ruettinger A, Kiselev M A, Wartewig S, Neubert R H H
Institute of Pharmacy, Martin Luther University Halle-Wittenberg, Halle-Saale, Germany.
Skin Pharmacol Physiol. 2008;21(2):58-74. doi: 10.1159/000112956. Epub 2008 Jan 11.
The stratum corneum (SC) represents the outermost layer of the mammalian skin, exhibits the main skin barrier and plays an important role in the water penetration pathway through the SC. Knowing the structure and properties of the SC at the molecular level is essential for studying drug penetration through the SC and for the development of new dermal drug delivery systems. Therefore, research interest is focused on the SC lipid matrix and on water diffusion through it. Thus, the ultimate aim is to design a lipid mixture that mimics the barrier properties of the human SC to a high extent and that can substitute the SC in drug delivery systems. This review summarizes various studies performed on either isolated animal or human ceramide based SC model systems, coming to the result that using synthetic lipids with a well-defined architecture allows good extrapolation to the in vivo situation. This review is the continuation of part 1 that is focused on a detailed description of the thermotropic and/or lyotropic phase behaviour of single ceramide types obtained by various experimental techniques. The objective of part 2 is to reflect the numerous studies on SC lipid model systems, namely binary, ternary and multicomponent systems, during the last decade. In this context, neutron diffraction as a prospective tool for analyzing the internal membrane structure is addressed in particular. Based on these new insights, current SC models are presented, whose validations are still under discussion. A profound knowledge about SC lipid organization at the molecular level is still missing.
角质层(SC)是哺乳动物皮肤的最外层,是主要的皮肤屏障,在水分透过角质层的途径中起重要作用。在分子水平上了解角质层的结构和特性对于研究药物透过角质层以及开发新的皮肤给药系统至关重要。因此,研究兴趣集中在角质层脂质基质及其水分扩散上。最终目标是设计一种脂质混合物,使其在很大程度上模拟人类角质层的屏障特性,并能在给药系统中替代角质层。本综述总结了对基于分离的动物或人类神经酰胺的角质层模型系统进行的各种研究,得出的结果是,使用具有明确结构的合成脂质能够较好地外推至体内情况。本综述是第1部分的延续,第1部分重点详细描述了通过各种实验技术获得的单一神经酰胺类型的热致和/或溶致相行为。第2部分的目的是反映过去十年中对角质层脂质模型系统(即二元、三元和多组分系统)的大量研究。在此背景下,特别讨论了中子衍射作为分析内膜结构的一种前瞻性工具。基于这些新见解,介绍了当前的角质层模型,其验证仍在讨论中。目前仍缺乏关于角质层脂质在分子水平上组织的深入知识。