葛根素脂质体滴眼液的制备及其药动学研究

Preparation and lacrimal pharmacokinetics of eye drops of puerarin liposomes in rabbit tears

目的:制备葛根素脂质体滴眼液,研究其在兔泪液中的消除情况。方法:采用逆相蒸发法制备葛根素脂质体;用葡聚糖凝胶柱分离脂质体和游离药物,测定葛根素在脂质体中的包封率;采用透射电子显微镜观察脂质体形态,激光粒度测定仪测定脂质体的粒径分布;以葛根素滴眼液为对照,HPLC法测定葛根素脂质体滴眼液在兔泪液中药物浓度,计算药物动力学参数。结果:葛根素脂质体形态圆整,平均粒径为195.7nm,药物包封率为48.3%,葛根素脂质体制剂在兔泪液中代谢药动学参数MRT,AUC分别为葛根素滴眼液的3.89和3.06倍。结论:成功制备了葛根素脂质体滴眼液,与普通滴眼液相比,显著提高了药物在泪液中的浓度,延长了平均滞留时间,提高了药物在眼部的吸收。

Objective ： To prepare eye drops of puerarin liposomes and investigate its lacrimal pharmacokinetics in rabbit tears. Method： Puerarin liposomes were prepared by reverse phase evaporation technique. The liposomes and free puerarin were separated by SephadexG-50 chromatography and then encapsulation ratio of liposomes was determined in detail. Micromorphology of liposome particles was observed by electronic transmission microscope and the size distribution of the liposomes was analyzed by laser particle size analyzer. The concentration of puerarin in rabbitg tears was determined by HPLC after ocular administration of 50 μL puerarin liposomes while puerarin eye drops was chosen as control with the same puerarin concentration. The pharmacokinetic parameters were calculated by software program 3P97 according to one-compartment mode. Result： Global liposome nanoparticles with diameter of about 195.7 nm were prepared successfully. The encapsulation ratio of puerarin in the liposomes was 48.3%. The mean residence time （MRT） value and the area under concentration （AUC） of puerarin in liposome were 3.89 and 3. 06 times more than those of puerarin eye drops. Conclusion： Liposomes as a drug carrier can greatly increase the concentration of puerarin in tears, enhance the pre-ocular retention time than that of eye drops.