影响主动载药法制备硫酸长春新碱脂质体包封率的因素

Study on influencing factors in preparation of vincristine sulfate liposomes by active loading method

目的采用主动载药法制备硫酸长春新碱脂质体,考察包封率的影响因素。方法采用阳离子交换树脂分离脂质体与游离药物,用HPLC测定包封率;考察了温度、pH调节剂、药脂比、包衣辅料及制备工艺对包封率的影响。结果脂质体的包封率随温度的升高而增加、随药脂比增大而降低、Na2HPO4最适合作pH调节剂;以pH梯度法和(NH4)2SO4梯度法制备的脂质体包封率分别为86.9%,70.8%;加入聚乙二醇单甲醚2000胆固醇琥珀酸酯(methoxypolyethyeneglycol2000cholesterylsuccinate,CHS-PEG2000),包封率提高到92.8%,97.6%。结论主动载药法适于制备硫酸长春新碱脂质体;温度,pH调节剂和药脂比是影响包封率的重要因素。

OBJECTIVE To prepare vincristine sulfate liposomes by active loading method, and study the influence of different factors on the entrapment efficiency. METHODS Cation exchange resin was used to separate the free vincristine sulfate from the liposomes. The entrapment efficiency was deternlined. The influences of various factors, including incubation temperature, the basic solution of external water phase, drug-to-lipid ratio, long-circalating materials and the methods of prepartion, on the entrapment efficiencies were investigated. RESULTS The entrapment efficiency was enhanced by the increased temperature and/he decreased drag-to-lipid ratio. Na2HPO4 was suitable for adjusting pH value in external water phase. The entrapment effieiencies with pH transmembrane gradients and arrunonium sulfate transmembrane gradients were 86.9% and 70.8 %, respectively, while up to 92.8 % and 97.6% with the incorporation of CHS-PE200（methoxypo/yethyene glycol 200 cho/estery/suecinate） in liposomal formulation. CONCLUSION Active loading method is suitable for pwparing vineristine sulfate liposomes. The factors of temperature, basic solution and drug-to-lipid ratio can influence liposomal entrapment efficiencies prominently.