Interactions of oleic acid and model stratum corneum membranes as seen by 2H NMR
Interactions of oleic acid and model stratum corneum membranes as seen by 2H NMR
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DOI：
10.1016/j.ijpharm.2005.10.008
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发表时间：
2006-01-13
影响因子：
5.8
通讯作者：
Thewalt, JL
中科院分区：
文献类型：
--
作者：
Rowat, AC;Kitson, N;Thewalt, JL
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这种含有胆固醇-d（6）、棕榈酸-d（31）或油酸-d（2）的多层SC分散体，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 ℃）的函数。我们的研究结果表明，低于40摄氏度，油酸（OA）是在一个“各向同性”相，表明它没有纳入层状膜相。在SC模型膜的结晶至液晶熔融温度T-m=40-42 ℃和以上，OA与层状SC膜相互作用，对OA浓度有轻微的依赖性。当SC模型膜暴露于OA时，T-m不改变，我们也没有看到标记的PA监测的膜链紊乱的任何显著变化。然而，棕榈酸（PA）和胆固醇SC模型膜组件的光谱包含一个各向同性的峰，随着温度的升高而增长。因此，我们的研究结果表明，油酸提取一部分的内源性SC膜成分，促进SC膜系统中的相分离。减少结晶脂质的比例和创造更具渗透性的富含OA的结构域是解释OA如何增强经皮渗透的合理机制。(C)2005 Elsevier B. V.保留所有权利。
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. (C) 2005 Elsevier B.V. All rights reserved.