硫酸铵梯度法制备盐酸拓扑替康脂质体及其在大鼠体内的药动学  

Preparation and Pharmacokinetics in Rats of Topotecan Hydrochloride Liposomes by Ammonium Sulfate Gradient Method

作　　者：许磊磊[1] 陈宪智[2] 李亚平[1,3] 顾王文 

机构地区：[1]江苏大学药学院,江苏镇江212013 [2]沈阳药科大学,辽宁沈阳117000 [3]中国科学院上海药物研究所药物制剂中心,上海201203

出　　处：《中国医药工业杂志》2014年第12期1139-1142,共4页Chinese Journal of Pharmaceuticals

摘　　要：采用硫酸铵梯度法,以氢化磷脂、胆固醇为脂质材料,制备了二硬脂酰磷脂酰乙醇胺-聚乙二醇修饰的盐酸拓扑替康脂质体。采用单因素法考察了处方工艺因素对包封率的影响,并比较了优化后制品与普通注射液在体外释放及大鼠体内药动学行为的差异。结果显示,按优化工艺制备的盐酸拓扑替康脂质体包封率为(93.14±1.52)%,平均粒径为69.6 nm,在10%胎牛血清中144 h才能完全释放,脂质体组AUC0→t是普通注射液的61倍。The topotecan hydrochloride liposomes modified with distearoyl phosphatidyl ethanolaminepolyethylene glycol（DSPE-PEG） were prepared by ammonium sulfate gradient method with hydrogenated phospholipids and cholesterol as lipid materials. The effects of formulation factors on encapsulation efficiency of the product were investigated by single factor tests. The differences of in vitro release and in vivo pharmacokinetics in rats between the optimal product and common injection were compared. The results showed that the encapsulation efficiency of the optimal product was（93.14±1.52）% with the mean particle size of 69.6 nm. The drug could completely release within 144 h in the medium containing 10% fetal bovine serum. Furthermore, the AUC0→t of the liposomes group was 61 times higher than that of the injection group.

关 键 词：硫酸铵梯度法 盐酸拓扑替康 脂质体 药动学 体外释放 

分 类 号：R944.9[医药卫生—药剂学]