拓扑替康脂质体的制备及体内分布研究  

Preparation and biodistribution of topotecan liposomes

作　　者：郝艳丽[1] 邓英杰[1] 陈妍[1] 左玉鹏 张勇[1] 

机构地区：[1]沈阳药科大学药学院,沈阳110016 [2]河南省灵宝市第一人民医院药剂科,灵宝472500

出　　处：《中国新药杂志》2006年第8期606-609,共4页Chinese Journal of New Drugs

基　　金：国家新药研究基金项目(94-97-20);辽宁省教育厅重大项目计划(202043233)

摘　　要：目的:制备由不同磷脂组成的盐酸拓扑替康脂质体,并比较其在荷瘤小鼠体内的分布行为。方法:采用非饱和的大豆卵磷脂(SPC)与饱和的氢化大豆卵磷脂(HSPC)作为包封材料,利用硫酸铵梯度法分别制备盐酸拓扑替康脂质体SPC-L与HSPC-L,静脉注射后测定荷瘤小鼠血浆及各组织中的药物浓度,研究其体内分布过程。结果:与游离药物相比,脂质体包封后拓扑替康的血浆浓度明显增加,SPC-L与HSPC-L组的血浆AUC 0-∞分别是游离药物组的7．0倍和18．8倍,同时其内酯／羧酸盐相对比例增加。肝、脾、肺以及肿瘤组织中药物浓度也明显增加,按每1．0 g组织中药物的量计算,HSPC-L组脾中的药物分布增加最多,是游离药物组的137．5倍;与SPC-L组比较,HSPC-L组肿瘤中的药物分布增加较多,相对于游离药物组的肿瘤摄取率为4．1。结论:脂质体包封改变了拓扑替康在体内的分布行为,与SPC-L比较,HSPC-L更为有效地提高了拓扑替康的体内稳定性,增加了其在血浆及各组织中的分布。Objective：To compare the biodistribution patterns of various topotecan HC1 liposomes made of different phospholipids in mice bearing sarcoma 180 （S 180） tumors, nethods：Topotecan HCl liposomes formulated with either unsaturated SPC （SPC-L） or saturated HSPC （HSPC-L） were prepared using an ammonium sulfate gradient method. The blood and tissue samples of the mice intravenously administered with either free topotecan or liposomal topotecan were collected to measure plasma concentrations and tissue distributions of these topotecans. Results： Compared with the free topotecan, the liposomes increased the plasma concentrations and the lactone/carboxylate ratio of topotecan. The AUC（0～∞） values of SPC-L and HSPC-L were 7-fold and 19-fold higher, respectively, than the free topotecan. The distributions of topotecan liposomes went up in liver, spleen, lung and tumor tissues. The HSPC-L was found to accumulate in spleen the most, showing an AUC value of 137.5 times as large as the free TPT. In addition, the HSPC-L was significantly accumulated in tumor tissues more than the SPC-L, and had a relative tumor uptake rate of 4.1 compared with the free topotecan. Conclusion：The liposomal encapsulation changed the distribution patterns of topotecan HC1 in vivo. The HSPC-L enhanced the topotecan stability and distribution more in vivo than the SPC-L.

关 键 词：盐酸拓扑替康 大豆卵磷脂 氢化大豆卵磷脂 脂质体 体内分布 

分 类 号：R944.1[医药卫生—药剂学] R979.1[医药卫生—药学]