制备单抗偶联载阿霉素白蛋白免疫毫微球的初步研究-东南大学学报医学版

制备单抗偶联载阿霉素白蛋白免疫毫微球的初步研究

单位：1. 东南大学医学院,江苏南京 210009;
2. 江苏省中医院核医学科,江苏南京 210029

分类号：R944.27; R979.14

出版年·卷·期（页码）：2012·31·第四期（393-397）

摘要：

目的:制备阿霉素牛血清白蛋白纳米粒(DOX-BSA-NP),观察其形态、粒径及药物缓释规律;制备并初步鉴定甲胎蛋白(AFP)单抗导向阿霉素白蛋白免疫毫微球(antiAFP- DOX-BSA-NP)。方法:以阿霉素、牛血清白蛋白为材料,采用去溶剂化法制备DOX-BSA-NP;使用电镜技术观察其形态及颗粒大小;采用胰蛋白酶消化方法测定其载药量和包封率,测定体外释药性质。采用SPDP交联法制备单抗导向的载阿霉素免疫毫微球,使用电镜技术观察其形态及颗粒大小,凝胶电泳测定共价连接。结果:(1) DOX-BSA-NP呈圆球状,外观呈红色;粒径大小均匀,载药量约为1.8%,包封率为90.3%,体外释药持续缓慢,第7天时,累积释药分数达到95%。(2) 采用SPDP交联方法制备的antiAFP-DOX-BSA-NP呈球形,粒径330~400 nm。结论:采用去溶剂化法可制备出具有缓释效果的阿霉素白蛋白微球;SPDP方法可以将单克隆抗体与载药微球连接制备出具有免疫功能的毫微球。

Objective: To prepare doxorubicin loaded bovine serum albumin nanoparticle (DOX-BSA-NP) and doxorubicin-loaded bovine serum albumin nanoparticle targeted at monoclonal antibody AFP (antiAFP-DOX-BSA-NP). Methods: DOX-BSA-NP was prepared by desolvation procedure and subsequent cross-linking of the wall material of bovine serum albumin. Calibration curve was constructed to calculate the content of doxorubicin in albumin microspheres. AntiAFP-DOX-BSA-NP was prepared by using methods of chemical cross-linking and its morphology was observed under electron microscopy. Results: The prepared albumin microspheres of doxorubicin had a size and was slowly released. The immuno-nanospheres also had a proper size for targeting the liver. Conclusion: The established process with the method of SPDP cross-linking is suitable for preparing smaller particle size microsphere for intravenous injection.

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