混合胶团增溶的环孢素A经小鼠皮肤的渗透作用

目的研究由不同表面活性剂和磷脂所组成的混合胶团(mixedmicelles)对环孢素A经小鼠皮肤给药的渗透促进作用。方法将含药混合胶团溶液封闭性应用于离体或在体小鼠皮肤,测定接收介质和血液中环孢素A含量。结果离体条件下,不同表面活性剂和磷脂所形成的混合胶团的皮肤渗透作用强度为:胆酸钠-磷脂混合胶团>脱氧胆酸钠-磷脂混合胶团>TritonX-100-磷脂混合胶团>Tween-20-磷脂混合胶团。在体条件下,用胆酸钠-磷脂混合胶团后,5h血药浓度达峰值,随后血药浓度缓慢下降。结论混合胶团在水溶液状态下对大分子难溶药物环孢素A具有一定的皮肤促渗效果。

TRANSDERMAL DELIVERY OF CYCLOSPORIN A SOLUBILIZED IN MIXED MICELLES THROUGH MICE SKIN

AIM To investigate the transdermal delivery effects of cyclosporine A solubilized in mixed micelles composed of phospholipid and different surfactants. METHODS When applied onto the excised abdominal skin of the mice occlusively, the enhancing effects of various mixed micelles on the penetration of cyclosporin A were assessed by an in vitro permeation technique. In vivo study was carried out by topical application of sodium cholate phospholipid mixed micelles onto the mice skin and drug blood concentration was detected. RESULTS In vitro , mixed micelles containing different surfactants displayed distinct permeability and corresponded to the following order: sodium cholate > sodium deoxycholate > Trition X 100 > Tween 20. In vivo , peak drug concentration was detected at 5 h and after that the concentration fell down slowly. CONCLUSION Mixed micelles were shown to be efficient carrier for the transdermal delivery of the lipophilic polypeptide when kept in solution during the application process.