黄体酮及其前体脂质体制剂的Caco-2细胞转运研究

Transport of Progesterone and Its Proliposome in Caco-2 Cells Monolayer

目的研究黄体酮及其前体脂质体制剂的胃肠吸收转运机制。方法采用Caco-2细胞模型考察黄体酮及其脂质体的转运,考察转运时间、药物浓度及抑制剂(环孢素和维拉帕米)对黄体酮转运的影响。结果黄体酮表观渗透系数随浓度变化而变化,抑制剂的加入会提高黄体酮的表观渗透系数,黄体酮脂质体能使黄体酮累积转运量提高,表观渗透系数明显增加,黄体酮脂质体的转运符合被动扩散特征。结论黄体酮的吸收受P-糖蛋白的介导,这可能是导致其生物利用度低的原因之一。黄体酮属生物药剂学分类系统中Ⅱ类药物,提高溶解度可提高其生物利用度,黄体酮脂质体能通过改变黄体酮的吸收机制,使黄体酮转运以被动扩散方式进行,从而明显促进黄体酮的吸收。

OBJECTIVE To study the absorption mechanism of progesterone and its proliposome in gastrointestinal （GI） tract. METHODS Caco-2 ceils monolayer was employed to investigate the transport of progesterone and its proliposome, and the effect of transport time, the drug concentration and inhibitors （cyclosporine and verapamil） on progesterone transport was further conducted. RE- SULTS The apparent permeability coefficient of progesterone changed with the variety of the drug concentration, and inhibitors could improve the accumulative transport flux and the apparent permeability coefficient of progesterone. Liposome could also increase the transport of progesterone. But the transport of progesterone liposome was complied with a passive diffusion. CONCLUSION The absorption process of progesterone is affected by P-gp, which may lead to its low bioavailability. As progesterone belongs to the second kind drugs in biopharmaceutical classification system, its bioavailability can be improved as the solubility is increased. Liposome can also improve its absorption and bioavailability through changing its absorption mechanism, which means the transport could be a passive diffusion.