聚乙二醇1000维生素E琥珀酸酯修饰多柔比星脂质体的制备和性质

Preparation and Characterization of TPGS-Modified Doxorubicin Liposomes

目的制备聚乙二醇1000维生素E琥珀酸酯(TPGS)修饰的脂质体,并对其理化性质进行考察。方法采用薄膜超声法制备脂质体,用硫酸铵梯度法制备将多柔比星载入脂质体内,阳离子交换树脂吸附法测定药物包封率,用透析法测定其体外释放,透射电镜观察脂质体形态,激光粒度测定仪测定粒度分布和Zeta电势,并考查脂质体稳定常数Ke、药物泄漏率以及胎牛血清对脂质体粒度的影响。结果 TPGS修饰的脂质体形态规整,药物包封率为(95±2.13)%(n=3);Zeta电位为-3.06mV,平均粒径为68.7 nm,多分散指数为0.186;TPGS修饰后能显著提高脂质体的贮藏以及在血清中的稳定性,大大降低药物泄漏率,而体外释放快于普通脂质体。结论 TPGS修饰的多柔比星脂质体具有包封率高、粒径小、稳定性好等优点。

OBJECTIVE To prepare doxorubicin liposomes modified by TPGS1000, and investigate their physicochemical properties. METHODS Liposomes were prepared by thin-film ultrasonic technology, and doxorubicin was remotely loaded by （NH4） 2S04-gradiend method. The encapsulation efficiency of doxorubicin was determined ＇after cationic resin absorption. Drug release in vitro was carried out with dialysis bag; the morphological characterization of liposomes was observed by transmission electron microscopy; particle size distribution and Zeta potential were determined by laser nanoparticles size analyzer; stability constant （Ke）, drug leakage and the influence of fetal bovine serum on the particle size distribution were also investigated. RESULTS TPGS-modified liposomes exhibited uniform shape with high drug encapsulation efficiency of （95 ±2. 13 ）% （n = 3 ）. The Zeta potential was about -3.06 mV, and mean diameter was 68.7 nm with polydispersity index of 0. 186. Compared to conventional doxorubiein liposomes, the modified liposomes exhibited significantly improved stability during storage as well as in serum. TPGS reduced drug leakage from liposomes during storage in spite of enhancing the release in vitro. CONCLUSION Doxorubicin liposomes modified by TPGS showed favorable properties including high encapsulation efficiency, small size and good stability.