鬼臼毒素二棕榈酸磷脂酰胆碱脂质体局部外用的实验研究

目的观察鬼臼毒素脂质体皮肤外用时的释药方式和药物在皮肤中的滞留量。方法以超声波法制备鬼臼毒素的二棕榈酸磷脂酰胆碱(DPPC)和大豆卵磷脂两种脂质体悬液,将相同浓度的鬼臼毒素酊剂及两种鬼臼毒素脂质体悬液涂于幼猪的背部皮肤上,以空白脂质体、空白酊剂作为对照。观察48 h内不同时间段、不同制剂中的鬼臼毒素在皮肤中的滞留量。结果鬼臼毒素酊剂在用药1 h后皮肤中出现药物高峰,随即很快下降;大豆卵磷脂脂质体鬼臼毒素在皮肤中缓慢释放,无明显药物高峰出现,药物浓度持续高于鬼臼毒素酊剂;DPPC脂质体鬼臼毒素用药后4 h在皮肤中出现药物高峰,然后缓慢下降至一定水平后,药物浓度维持稳定,48 h内药物浓度一直显著高于鬼臼毒素酊剂及鬼臼毒素大豆卵磷脂脂质体。结论DPPC脂质体包裹鬼臼毒素外用具有更好的皮肤靶向性,是较好的皮肤外用制剂。

Experimental study of podophyllotoxin dipalmitoylphosphatidylcholine liposome for topical skin application

Objective To observe the drug release of podophyllotoxin liposome and the drug retention in the skin. Methods Two liposome suspensions containing respectively podophyllotoxin dipalmitoylphosphatidylcholine (DPPC) and soya bean lecithin were prepared ultrasonically. Podophyllotoxin anhydride and the liposome suspensions were applied onto the skin of young pigs to observe the drug retention in the skin at different time points in the following 2 days, with exclusive liposome or anhydride serving as control. Results One hour after application of podophyllotoxin anhydride, a peak of the drug concentration in the skin occurred followed by immediate declination, a process not observed after the application of bean lecithin liposome due to gradual drug release that produced drug concentration constantly much higher than that of podophyllotoxin anhydride. A peak concentration was also observed 4 h after application of podophyllotoxin DPPC liposome, which then declined slowly to and stablized at a higher level than that of bean lecithin liposome of anhydride within 48 h. Conclusion DPPC liposome-embedded podophyllotoxin better targets the drug to the skin after application, and is a suitable preparation for topical skin application.