角质层及其类脂对雌二醇经皮渗透的作用

采用扩散装置和放射性同位素标记物测定,辅以FTIR和DSC技术,研究了雌二醇(OE)在角质层、去脂角质层、表皮以及活性表皮中的渗透性质和分配性质,分析角质层及其类脂在亲脂性药物经皮渗透中的作用。实验表明角质层是该类药物渗透的屏障,OE在其中的渗透速度受到角质层通透性和药物在角质层分配系数的双重控制,而OE从角质层转运至活性表皮的过程不成为限速因素。角质层的屏障性质仅部分来源于角质层类脂,而角质层细胞膜产生的阻力则是角质层屏障性质的重要组成部分。角质层类脂同时又可能是OE扩散的途径,该类物质通过对亲脂性药物增溶、提高后者在角质层中的分配产生影响。促进剂1,8-桉油精(1,8-CN)对OE的促渗作用也部分地依赖于角质层类脂的存在,通过一种可逆的物理相互作用改变类脂途径的通透性。

Essential Effect of Stratum Corneum and Its Lipids on Permeability of Oestradiol through Human Skin

The effect of stratum corneum(SC) and its lipids in human skin permeation was assessed in ritro in a diffusion system, combined with the determination of partition coefficients. OE and 1, 8-CN were used as the model lipophUie drug and penetration enhancer respectively. The results showed SC contstituted the main barrier of OE penetrating through skin, its permeability was controlled by both the tissue resistance and partitioning behaviour of OE in SC. However, OE transporting process between SC and living epidermis did not be found to be the rate-limited factor. Both lipids and cells were responsible for the formation of SC barrier characteristics, but SC lipids may also play a role in solubilization of lipophilic drug in SC, and reversely interact with penetration enhancer, so as to become the possible route and contribute towards the improvement of OE penetration.