盐酸万古霉素阳离子脂质体的制备及其性质研究

Preparation and properties of cationic liposomal vancomycin

目的制备万古霉素阳离子脂质体(cationic liposomal vancomycin,CLVs),确定其最佳处方制备工艺,并研究其性质。方法采用正交法确定逆相蒸发法制备CLVs的最佳处方;采用HPLC法测定药物含量;用微型葡聚糖凝胶柱分离脂质体混悬液中的CLVs与游离药物;在电镜下观察CLVs的形态,并采用激光散射法测定其粒径和Zeta电位。结果制备的CLVs为多囊脂质体;通过正交实验,确定逆相蒸发法制备CLVs的最佳处方为∶磷脂∶硬脂酰胺∶胆固醇的摩尔比为7∶3∶1,脂质∶药物的质量比为15∶1,有机相∶水相的体积比为3∶1;制备的脂质体平均粒径、Zeta电位、pH值以及包封率分别为(185.75±16.33)nm、(69.11±4.62)mV、(6.98±0.01)和(8.58±0.045)%,脂质体在4℃和-80℃条件下保存3个月,稳定性良好,药物泄漏率<5.0%。结论采用逆相蒸发法制备万古霉素阳离子脂质体,方法简便,重现性好,包封率较高。

Objective To prepare cationic liposomal vancomycin（CLVs）,optimize its formulations and study its characteristics.Methods CLVs was prepared by modified reverse phase evaporation method,and separated from the suspention with Sephadex G-50 minicolumns.The optimum lipid composition was screened by orthogonal design.CLVs′ shape was observed in EM,and its particle size and Zeta potential were measured with laser scattering method.Results The optimized lipid composition for preparing CLVs was composed of soya phosphatidylcholine,stearamide and cholesterol at the molar ratios of 7∶3∶1.the proportion of lipid composite vancomycin was 15∶1,the proportion of organic phase and aqueous phase was 3∶1.The mean value of particle size,Zeta potential and entrapment efficiency of CLVs were（185.75±16.33） nm,（69.11±4.62）mV and（8.58±0.045）%,respectively.The CLVs was stored for three months at 4 ℃ and-80 ℃,which appeared steady with leak ratio below 5%.Conclusion The modified reverse phase evaporation method was a simple,reproducible method to prepare CLVs.