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半乳糖化白蛋白磁性阿霉素纳米粒制备工艺的优化

Preparation galactosyl-HSA-magnetic-adriamycin-nanoparticles (ADR-GHMN) and its physical property study

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【作者】 张阳德翟登高龚连生席浩潘一峰李浩刘勤黄林吴泽建

【Author】 ZHANG Yang-de1, ZHAI Deng-gao1, GONG Lian-sheng1, XI Hao1, PAN Yi-feng2, LI Hao2, LIU Qin2, HUANG LIN2, WU Ze-jian2(1. National Hepatobiliary and Enteric Surgery Research, Xiangya Hospital of Central South University, Changsha, Hunan 410008, P.R.China; 2. Key Laboratory Of Nanobiological Technology Ministry of Health, P.R.China, Changsha, Hunan, 410078, P.R.China)

【机构】 中南大学湘雅医院卫生部肝胆肠研究中心卫生部纳米生物技术重点实验室卫生部纳米生物技术重点实验室 湖南长沙410008湖南长沙410008湖南长沙410078湖南长沙410078

【摘要】 目的制备具有稳定磁性、能够携带化疗药物的半乳糖化白蛋白磁性纳米粒,并对纳米粒的磁性、药物含量、包封率、粒径大小等物理性质进行检测。方法运用正交试验设计方法设计实验,以粒径大小、纳米药物的载药量和包封率3个指标考察固化温度、固化时间、搅拌速度及糖化比率四个因素的四个水平,从中选出最优化组合,并以最优化组合重复实验,验证试验条件的稳定性以及实验的可重复性。先行制备半乳糖化白蛋白,将阿霉素、半乳糖化白蛋白、磁粉按一定比例混合,通过在精制棉仔油中超声乳化、加热变性固化、乙醚洗涤等工艺制作出载药纳米粒,用乙醇提取法提取纳米粒中的阿霉素,并用紫外分光光度计测定含量,激光粒度分析仪分析粒径大小。结果运用最优化条件制备的纳米粒,其平均粒径为(197±32)nm,载药量(48.79±4.47)ug/mg,包封率(94.34±3.32)%。结论上述优化条件稳定,试验的可重复性高。

【Abstract】 Objective: To prepare galactosyl-HSA-magnetic-adriamycin-nanoparticles (ADR-GHMN), measure physical property of the ADR-GHMN, such as magnetism, galactose density (GD), drug loading (DL) and size of nanoparticles. Methods: Designing the experiment adepted the method of orthogonal design, through evaluating the nanoparticles from the drug loading (DL), size of nanoparticles and trap efficiency, and observed effection of solidification temperature, solidification time, mix speed and galactose density on the four level in the course of preparing ADR-GHMN, respectively. From the four level, the best one was chosen, and was repeated experiment to verify repeatable and stabilities of this experimental condition. First we prepare galactosyl-HSA, then mix the galactosyl-HSA, adriamycin and magnetites poweder according to appropriate proportion. Then the nanoparticles were produced by sonication in oil, heat polymerization and washing with aether. Results:Nanoparticles of preparation used the above method, average size were (197±32)nm, drug loading (48.79±4.47)ug/mg, trap efficiency (94.34±3.32)%. Conclusion: Above-mentioned optimum condition are steady and have high rate of repetition ability of the experiment.

【基金】 国家“十五”863计划课题:“磁性纳米药物载体系统治疗肝脏恶性肿瘤研究”项目编号:2002AA214011
  • 【文献出处】 中国医学工程 ,China Medical Engineering , 编辑部邮箱 ,2004年04期
  • 【分类号】TQ465
  • 【被引频次】8
  • 【下载频次】180
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