阿霉素人血清白蛋白微球的制备及其性质的初步研究  

Preliminary Study on Preparation and Pharmaceutic Features of Adrimycin-loaded Human Serum Albumin Microspheres

作　　者：刘晓波[1] 蔡美英[1] 龚艳[2] 张志荣[2] 魏大鹏[1] 王霞[1] 黎光[1] 

机构地区：[1]四川大学华西基础医学与法医学院免疫学教研室,成都610041 [2]四川大学华西药学院药剂学教研室

出　　处：《四川大学学报（医学版）》2004年第1期107-109,137,共4页Journal of Sichuan University(Medical Sciences)

基　　金：卫生部科研基金 (编号 98-1-2 2 5 );四川省卫生厅基金资助

摘　　要：目的　制备载阿霉素人血清白蛋白微球 (ADR- HSA- MS) ,并研究其药剂学性质和体外对肿瘤细胞的细胞毒作用。方法　以阿霉素 (ADR)、人血清白蛋白 (HSA)为材料 ,采用乳化高温固化法制备 ADR- HSA- MS;采用光镜、电镜技术观察 ADR- HSA- MS的形态 ;采用胃蛋白酶消化法、动态透析法分别测定 ADR- HSA- MS的载药量 ,体外释药性质 ;采用 MTT比色分析法测定 ADR- HSA- MS对人肝癌株 SMMC- 772 1细胞的细胞毒作用。结果ADR- HSA- MS圆球状 ,表面较光滑 ,平均粒径为 1.2 μm,外观为红色 ;ADR- HSA- MS表观载药量为 2 .73% ,有效载药量为 1.6 9% ,释药呈持续缓慢状态 ,至 5 d时 ,其累积释药分数达 5 0 % ,最大累积释药分数为 6 5 % ;ADR- HSA-MS与 SMMC- 772 1人肝癌细胞孵育 4 d后 ,对 SMMC- 772 1细胞具明显杀伤作用 ,在 0 .3～ 2 .5 μg/ m l ADR质量浓度范围内呈一定剂量依赖性 ,其杀伤曲线与游离 ADR接近。结论　采用乳化高温固化法能制备出具缓释性质的载阿霉素人血清白蛋白微球。Objective To prepare adrimycin-loaded human serum albumin microspheres(ADR-HSA-MS) and to study its pharmaceutic properties and in vitro cytotoxicity.Methods ADR-HSA-MS,consisting of ADR and HSA, were prepared by emulsion heating solidification method and its morphology was observed by optical microscopy and scanning electron microscopy. Pepsin digestion method was used for determining drug loading of ADR-HSA-MS and membrane diffusion technique for detection of in vitro release of ADR from the microspheres. MTT colorimetric assay was used to determine cytotoxicity of ADR-HSA-MS for human hepatoma SMMC-7721 cell line.Results ADR-HSA-MS looked like smooth red spheres with an average diameter of 1.2 μm and had an apparent drug-loading of 2.73% or an effective drug-loading of 1.69%. Its peak of the accumulated drug-releasing fraction was 65%, and 50% of ADR releasing from the MS would take five days,which suggested a slow release of ADR from the albumin microspheres. ADR-HSA-MS exerted remarkable cytotoxicity to human hepatoma SMMC-7721 cells with dose-dependence at a range of ADR concentration from 0.3 μg/ml to 2.5 μg/ml when incubated with the target cells for four days.Its killing curve was similar to that of free ADR.Conclusion Emulsion heating solidification method could be used for preparation of adrimycin-loaded human serum albumin microspheres with sustained release property.

关 键 词：阿霉素 人血清白蛋白 微球 缓释 

分 类 号：TQ464[化学工程—制药化工]