改良pH梯度法制备盐酸小檗碱脂质体

Preparation of Berberine Hydrochloride Liposomes by a New pH Gradient Method

目的制备盐酸小檗碱脂质体,并考察其包封率的影响因素。方法采用离子交换法建立跨膜pH梯度并制备盐酸小檗碱脂质体;以紫外分光光度法和激光粒度仪分别测定脂质体的包封率和粒径;考察外水相pH、pH调节剂、磷脂种类、载药温度与时间、加药顺序及药脂比对包封率的影响。结果包封率随外水相pH的升高而增加;最佳pH调节剂为磷酸盐缓冲液;磷脂为氢化大豆卵磷脂时包封率最高;随载药温度的升高和载药时间的增加包封率有提高的趋势,但基本不受加药顺序的影响;最佳药脂比为1∶10。在最优处方工艺下盐酸小檗碱脂质体的包封率为(98.6±0.68)%(n=3),平均粒径为124.1 nm。结论改良pH梯度法制备的盐酸小檗碱脂质体包封率高,重现性好。

OBJECTIVE To prepare berberine hydrochloride liposomes and investigate the influence of different factors on the entrapment efficiency. METHODS Berberine hydrochloride liposomes were prepared by a novel pH gradient method. The transmembrahe gradient was set up by ion exchange resin. UV-visible spectrophotometry and laser particle analyzer were applied to determine the entrapment efficiency and the size of berberine hydrochloride liposomes, respectively. The influences of various factors, including exterior pH values, the basic solutions of external water phase, phospholipids, incubation temperature and time, adding sequence and the ratio of drug to lipid, on the entrapment efficiency were investigated. RESULTS Entrapment efficiency increaced with higher pH values, the best basic solution is phosphate buffer and HSPC is the most suitable phospholipid, the entrapment efficiency was enhanced by increacing incubation temperature and time, not affected by adding sequence, and the optimal ratio of drug to lipid was 1 ： 10. The entrapment efficiency of berberine hydrochloride liposomes under the optimum conditions was （98.6 ± 0. 68 ） % （ n = 3 ）, and the mean diameter was 124. 1 ran. CONCLUSION The berberinc hydroehloride liposomes with high entrapment efficiency are prepared by a novel pH gradient method, and the method is proved to be feasible.