油酸经皮促透作用微观机理的研究

皮肤角质层是药物透皮吸收的主要屏障，而角质层类脂在角质层的屏障功能中起着主要的作用。本文的主要目的是研究透皮促进剂油酸导致角质层类脂形态上的变化及其降低表皮屏障功能的机理。10%的油酸/丙二醇应用于雄性Wistar大鼠的表皮2h，标本用四氧化钌固定后，电镜观察表明由于油酸的作用导致角质层类脂膜结构发生了显著的变化，破坏了其类脂膜的有序结构并在角化细胞间隙中形成大量腔隙。表明透皮促进剂油酸的主要作用机理是破坏角质层类脂膜结构及在角质层细胞间形成腔隙，因而增加表皮的通透性。

Mechanism of oleic acid-induced percutaneous penetration enhancement: an ultrastructural study

The major function of the epidermis is to form a protective layer,the stratum corneum,presents a significant barrier to the transdermal drug delivery. Penetration enhancer such as oleic acid,which increase skin permeability,appear to act on the stratum corneum lipids representing the principle regulatory channel for the penetration of small molecules. The purpose of present study was to assess the interaction between penetration enhancer of oleic acid and stratum corneum lipids as well as its mechanism of penetration enhancement in vivo. Wister mice were treated topically with oleic acid in propylene glycol for 2h and the structure of stratum corneum intercellular lipid lamellae was examined by electron microscopy,using ruthenium tetroxide postfixation technique. Ultrastructural observations demonstrated both of the marked disorganization of the intercellular lipid lamellae and of the presence of distended lacunae within the stratum corneum. These results demonstrated that oleic acid induced skin penetration enhancement results from a mechanism involving the perturbation of stratum corneum lipid lamellae,and the lacunar domains might comprise a pore pathway for penetration of molecules across the stratum corneum.