Rowat Amy C, Kitson Neil, Thewalt Jenifer L
MEMPHYS, Department of Physics, University of Southern Denmark, Campusvej 55, 5230 Odense M, Denmark.
Int J Pharm. 2006 Jan 13;307(2):225-31. doi: 10.1016/j.ijpharm.2005.10.008. Epub 2005 Nov 15.
We have investigated the mechanism through which the penetration enhancer oleic acid acts on stratum corneum (SC) model membranes (bovine brain ceramide:cholesterol:palmitic acid, 1:1:1 molar ratio). We used solid state deuterium nuclear magnetic resonance to monitor such multilamellar SC dispersions containing either cholesterol-d(6), palmitic acid-d(31), or oleic acid-d(2) as a function of both fatty acid concentration (2:2:1:1 and 1:1:1:1 bovine brain ceramide:cholesterol:palmitic acid:oleic acid) and temperature (18-75 degrees C). Our results show that below 40 degrees C, oleic acid (OA) is in an 'isotropic' phase, indicating that it has not incorporated into the lamellar membrane phase. At and above the SC model membrane's crystalline to liquid crystalline melting temperature, T(m)=40-42 degrees C, OA interacts with lamellar SC membranes with a slight dependence on OA concentration. T(m) does not change upon the exposure of the SC model membrane to OA, nor do we see any significant change in membrane chain disorder as monitored by the labelled PA. However, the spectra of both the palmitic acid (PA) and cholesterol SC model membrane components contain an isotropic peak that grows with increasing temperature. Our results thus indicate that oleic acid extracts a fraction of the endogenous SC membrane components, promoting phase separation in the SC membrane system. Reducing the proportion of crystalline lipids and creating more permeable OA-rich domains is a plausible mechanism that explains how OA enhances transdermal penetration.
我们研究了渗透促进剂油酸作用于角质层（SC）模型膜（牛脑神经酰胺：胆固醇：棕榈酸，摩尔比1:1:1）的机制。我们使用固态氘核磁共振来监测此类包含胆固醇 - d(6)、棕榈酸 - d(31)或油酸 - d(2)的多片层SC分散体，其作为脂肪酸浓度（2:2:1:1和1:1:1:1牛脑神经酰胺：胆固醇：棕榈酸：油酸）和温度（18 - 75摄氏度）的函数。我们的结果表明，在40摄氏度以下，油酸（OA）处于“各向同性”相，表明它尚未掺入层状膜相。在SC模型膜的结晶态到液晶态的熔化温度T(m)=40 - 42摄氏度及以上时，OA与层状SC膜相互作用，对OA浓度有轻微依赖性。将SC模型膜暴露于OA时，T(m)不变，通过标记的PA监测，我们也未看到膜链无序有任何显著变化。然而，棕榈酸（PA）和胆固醇SC模型膜成分的光谱都包含一个随温度升高而增大的各向同性峰。因此，我们的结果表明，油酸提取了一部分内源性SC膜成分，促进了SC膜系统中的相分离。降低结晶脂质的比例并形成更多富含OA的可渗透区域是一种合理的机制，解释了OA如何增强透皮渗透。
