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pH敏感型磁性纳米树状大分子材料的制备及其性能研究

发布时间:2018-10-14 16:22
【摘要】:近年来智能响应型纳米药物在药物释放控制体系中受到广泛关注。它对于控制药物释放速度、减小药物的副作用等有重要意义。而针对人体不同组织结构微环境的pH微小变化(正常组织细胞的pH值接近中性,而病变组织细胞的pH值在5.5-6.9之间),pH响应的智能靶向药物逐步成为关注的热点。本文制备出一种分散性好、体外细胞毒性低的pH敏感型磁靶向纳米载体,并对它的载药性能进行了研究。主要工作如下:1.采用发散法制备了0.5G到2.5G的聚酰胺-胺(PAMAM)树枝状大分子,并根据产品的产率和纯度分析出PAMAM合成的最佳条件为:最佳温度25℃,最佳反应时间24h,最佳的投料比例为mol上一代PAMAM:molEDA/MA=1:24。2.分别采用水热法和化学共沉淀法制备出分散性良好的磁性Fe304纳米粒子,并对其表面进行改性,制备出亲水的氨基化Fe3O4。表征结果表明:经过APTES改性后得到的氨基化Fe304为分散性较好的球形粒子,粒径约17nm,磁含量为81%,具有良好的磁响应性能。3.实验分别用逐步接枝法和一步接枝法来将2.5G PAMAM接枝到氨基化Fe304上,并用水合肼改性端基为肼基(-NH-NH2),得到的复合粒子(Fe304-PAMAM-H)可以作为负载阿霉素的载体。表征结果表明:两种方法均有PAMAM接枝到磁性粒子上,表面接枝并未改变Fe304磁性粒子的晶型,且一步接枝法得到的复合粒子表面接枝更多,体外细胞毒性低,可以被视为安全的药物载体。4.阿霉素通过pH敏感的腙键负载到磁性纳米树枝状大分子载体上,制备出pH敏感型磁靶向载药体系。表征结果表明:一步接枝法制备出的Fe304-PAMAM-H具有比较高的载药率和包封率,且载药体系药物的释放对pH敏感,能有效的杀死肿瘤细胞。
[Abstract]:In recent years, intelligent responsive nanopharmaceuticals have attracted wide attention in drug release control systems. It is of great significance to control the drug release rate and reduce the side effects of drugs. However, the small changes of pH in different microenvironments of human tissues (the pH value of normal tissue cells is close to neutral, while the pH value of pathological tissue cells is between 5.5-6.9), pH response intelligent target drugs gradually become the focus of attention. In this paper, a pH sensitive magnetic targeting nano-carrier with good dispersion and low cytotoxicity in vitro was prepared and its drug loading properties were studied. The main work is as follows: 1. Poly (amide-amine) (PAMAM) dendrimers of 0.5G to 2.5G were prepared by divergence method. According to the yield and purity of the product, the optimum conditions for the synthesis of PAMAM were obtained as follows: optimum temperature 25 鈩,

本文编号:2270984

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