Azone类透皮剂作用机理及一种新型模型膜的研究

A NEW MODEL MEMBRANE AND ITS APPLICATION IN SKIN PENETRATION MECHANISM STUDIES OF AZONE

使用电子自旋共振波谱技术,采用5—doxyl stearic acid作为自旋标记物,新设计的镶嵌JPM和胆固醇的卵壳膜作为实验模型膜,进行Azone类透皮吸收促进剂的主要作用机理研究.实验证实上述膜是一种很有前途的模型膜.由于Azone透皮剂的作用,增大膜中类脂和自旋标记物的脂肪长链的运动速率,即增强类脂的流动性,使得类脂的序参数值减小,从而证实了前人有关角质化细胞间的类脂相是药物穿透角质层的主要通道的假设.为进一步探讨透皮剂对天然皮肤的作用,采用裸鼠皮肤角质层作为实验模型膜,得到与上述实验相符的结果.

A new-designed egg membrane is proved to be a promising model in skin penetration studies. By use of 5-doxyl stearic acid as spin label for ESR spectra measurement, Azone as skin penetration enhancer and egg membrane incorporated with IPM and cholesterol as experimental model, the major penetration enhancement mechanism of Azone had been assessed. A decrease in order parameter of lipid in the presence of Azone is due to increased motion rate of long hydrocarbon chain both in lipids and 5-doxyl stearic acid. It indicates an increased fluidity of the lipids incorporated into egg membrane because of the effect of Azone, that provides evidance to support hypothes considering the intercelluar lipid to be a major pathway for percutaneous absorption of drugs.The results obtained were confirmed by the use of bare-mouse skin stratum as experimental model which may allow to model the conditions in vivo penetration.