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目的 制备抗体偶联的阿霉素人血清白蛋白微球 ;评价该免疫微球的药剂学性质。方法 采用SPDP法将人肝癌单抗HAb1 8与阿霉素人血清白蛋白微球 (ADR HSA MS)共价偶联构建人肝癌特异性免疫微球 (HAb1 8 ADR HSA MS) ;采用玻片凝集法 ,免疫荧光染色法评价抗体与微球的交联 ;采用胃酶消化法 ,动态透析法分别测定免疫微球的载药量 ,体外释药性质 ;采用MTT比色分析法测定免疫微球经胃酶消解所释放ADR的细胞毒作用。结果 HAb1 8 ADR HSA MS的玻片凝集反应 ,免疫荧光染色均为阳性 ;ADR的平均回收率为 (98.95± 0 .96) % ;HAb1 8 ADR HSA MS表面光滑 ,圆球状 ,平均粒径 1 .2 μm ,有效载药量 1 .44 % ,最大累积释药分数为 41 % ;HAb1 8 ADR HSA MS的胃酶消解液在 50 0nm波长处有最大吸收 ,对人肝癌细胞株SMMC 772 1的杀伤作用曲线相似于ADR HSA MS及游离ADR。结论 采用SPDP法能将人肝癌单抗HAb1 8结合到阿霉素人血清白蛋白微球表面 ;该交联对免疫微球的有效载药量 ,最大累积释药量有一定程度影响 ,但对微球中ADR的药效性质没有影响
OBJECTIVE To prepare antibody-conjugated doxorubicin-human serum albumin microspheres and to evaluate its pharmacological properties. Methods Human hepatoma-specific immunoglobulin microspheres (HAb1 8 ADR HSA MS) were covalently coupled to human hepatoma McAb HAb1 8 and ADR HSA MS by SPDP. Immunofluorescence staining method to evaluate the antibody and microsphere cross-linking; using gastric enzyme digestion, dynamic dialysis were measured the amount of drug-loaded microspheres, drug release in vitro; using MTT colorimetric assay of immune microspheres Gastrointestinal digestion releases ADR cytotoxicity. Results The results of slide agglutination and immunofluorescence staining of HAb1 8 ADR HSA MS showed that the average recovery of ADR was (98.95 ± 0.96)%. The surface of HAb1 8 ADR HSA MS was smooth, spherical and the average particle size was 1. 2 μm, the effective drug loading was 1.44% and the maximum cumulative drug release fraction was 41%. The gastric enzyme digestion solution of HAb1 8 ADR HSA MS had the maximum absorption at 50 0 nm, killing human hepatocellular carcinoma cell line SMMC 772 1 The action curve is similar to ADR HSA MS and free ADR. Conclusion The SPDP method can bind human hepatoma McAb HAb1 8 to doxorubicin-human serum albumin microspheres. The cross-linking can affect the effective drug loading and the maximum cumulative release of immunoglobulin microspheres to some extent. However, The pharmacodynamic properties of ADR in the microspheres have no effect