Ping Q N, Sun G Q, Liu G J
Department of Pharmaceuticals, China Pharmaceutical University, Nanjinjg.
Yao Xue Xue Bao. 1993;28(12):924-30.
The role of stratum corneum (SC) and its lipid constituents in skin permeability was assessed in vitro in diffusion system combined with the determination of partition coefficients (PC) and DSC technique. 5-Fu and 1,8-CN were used as the hydrophilic drug and penetration enhancer, respectively. The results showed that the PCs of 5-Fu were the same in SC, delipid SC, full skin and SC-stripped full skin, but the diffusion coefficients (D) of 5-Fu were different from each other. They were 1.32 +/- 0.37 x 10(-7), 13.71 +/- 5.12 x 10(-7), 1.01 +/- 0.31 x 10(-7) and 540.85 +/- 50.99 x 10(-7) cm2/h, respectively. When the skin membranes were pretreated with 1,8-CN for 12 h, the PCs were reduced to similar extent. However, the D was increased significantly in SC and in full skin, there was a small increase for delipid SC. No change was found in the D of stripped skin. DSC analysis indicated that 1,8-CN might change the thermal behaviour of SC lipid and the influence disappeared when SC was extracted with organic solvent. These results suggest that SC was the main barrier for 5-Fu diffusion through human skin, and the intercellular lipids played an important role for the hydrophilic drug penetration regardless of the presence of the enhancer in SC.
采用结合分配系数（PC）测定和差示扫描量热法（DSC）的扩散系统，在体外评估了角质层（SC）及其脂质成分在皮肤通透性中的作用。分别使用5-氟尿嘧啶（5-Fu）和亲水性药物及1,8-桉叶素（1,8-CN）作为渗透促进剂。结果显示，5-Fu在SC、脱脂SC、全皮和去皮全皮中的PC相同，但5-Fu的扩散系数（D）彼此不同。它们分别为1.32±0.37×10⁻⁷、13.71±5.12×10⁻⁷、1.01±0.31×10⁻⁷和540.85±50.99×10⁻⁷ cm²/h。当皮肤膜用1,8-CN预处理12小时时，PC降低到相似程度。然而，SC和全皮中的D显著增加，脱脂SC中有小幅增加。去皮皮肤的D未发现变化。DSC分析表明，1,8-CN可能改变SC脂质的热行为，当用有机溶剂提取SC时，这种影响消失。这些结果表明，SC是5-Fu透过人皮肤扩散的主要屏障，无论SC中是否存在促进剂，细胞间脂质在亲水性药物渗透中都起重要作用。
