Drug permeation across the skin: effect of penetrant hydrophilicity.
Drug permeation across the skin: effect of penetrant hydrophilicity.
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药物透过皮肤渗透：渗透亲水性的影响。
DOI：
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发表时间：
1987
期刊：
影响因子：
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通讯作者：
Y. Chien
中科院分区：
文献类型：
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作者：
K. Tojo;C. Chiang;Y. Chien
孕酮本身是一种亲脂性类固醇，通过在甾体骨架的不同位置引入一个或多个羟基取代基，其亲水性逐渐增加。这些亲水性取代基对孕酮在无毛小鼠的完整皮肤和剥离皮肤的渗透的影响进行了研究，使用流体动力学良好校准的体外皮肤渗透系统。发现穿过完整皮肤和剥离皮肤的稳态渗透速率分别与药物在角质层或活皮肤中的溶解度大致成比例。此外，孕酮及其羟基衍生物在角质层中的溶解度随着渗透剂亲水性的增加而逐渐降低。这一发现与先前报告的药物渗透通过亲脂性硅胶膜的研究结果相似。然而，观察到这些孕激素在活的皮肤中的溶解度不仅取决于渗透剂的亲水性，而且取决于渗透剂分子上OH基团的位置。黄体酮及其羟基衍生物在角质层和活性皮肤中的扩散率几乎与药物的亲水性无关。
The hydrophilicity of progesterone, a lipophilic steroid itself, was progressively increased by incorporating one or more hydroxy substituents at different positions on the steroidal skeleton. Effects of these hydrophilic substituents on the permeation of progesterone across the intact skin and stripped skin of the hairless mouse were studied using a hydrodynamically well-calibrated in vitro skin permeation system. The steady-state rate of permeation across the intact skin and stripped skin was found to be approximately proportional to the solubility of drugs in the stratum corneum or in the viable skin, respectively. Furthermore, the solubility of progesterone and its hydroxyl derivatives in the stratum corneum was noted to decrease gradually as the hydrophilicity of the penetrant increased. This finding was similar to that of a previously reported study of drug permeation across the lipophilic silicone membrane. However, the solubility of these progestins in the viable skin was observed to be dependent not only on the penetrant hydrophilicity but also on the position of the OH group on the penetrant molecule. The diffusivity of progesterone and its hydroxyl derivatives across the stratum corneum and viable skin was almost independent of the hydrophilicity of the drugs.