阿霉素人血清白蛋白微球的制备及其性质的初步研究

目的 制备载阿霉索人血清白蛋白微球(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 以阿霉索(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-7721细胞的细胞毒作用。结 ADR-HSA-MS圆球状，表面较光滑，平均粒径为1．2μm，外观为红色；ADR-HSA-MS表观载药量为2．73％，有效载药量为1．69％，释药呈持续缓慢状态，至5d时，其累积释药分数达50％，最大累积释药分数为65％；ADR-HSA-MS与SMMC-7721人肝癌细胞孵育4d后，对SMMC-7721细胞具明显杀伤作用，在0．3～2．5μg／ml 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。

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

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 microns 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 microgram/ml to 2.5 micrograms/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.