两亲性梳型聚合物的制备及其药物载体的应用-化学专业论文.docxVIP

I I 摘 要 本文是以聚乙二醇单甲醚为反应物，制备端氨基聚乙二醇单甲醚，并以此做为引 发剂，引发 γ-炔丙基-L-谷氨酸-N-羧基内酸酐开环聚合反应。产物为聚氨基酸聚乙二醇 两亲性嵌段共聚物。并以此为基础，谷氨酸链段的炔基端用 click 方法链接，带有二硫 键标记的还原响应性聚合物链段。同时，同样的方法制备无响应性的一组聚合物作为 对比。两亲性梳型嵌段聚合物是生成产物，这种聚合物在水溶液可以自主装，形成可 降解的，两亲性的，高分子纳米药物载体胶束。它可以完成抗癌药物的包覆，运输， 和对所载药物的控释。与传统的药物载体相比，其具有更强的稳定性和更高的所载药 物释放率。其中带有还原响应性的胶束材料，可以根据环境中还原型谷胱甘肽（GSH） 的浓度变化，对所载药物进行智能的选择性控释。 实验通过 HNMR、FT-IR、GPC 对最终合成的材料进行了表征。通过 PTI 荧光系 统分别测定并计算得出：该材料临界胶束浓度接近或达到 10-4 数量级；载药率最高可 达到 24%左右；并且实验采用盐酸阿霉素作为所载药物，进行药物体外释放实验中得 出，其中还原响应性载药胶束在 GSH 浓度 10mmol/ml 时，最高的释放率达到 70%。在 动态光散射粒度仪的检测结果中：载药后胶束粒径范围在 70-90nm；并测得，未载药 具有还原响应性胶束材料，在 10mmol/ml GSH 环境中随时间延长，粒径分布范围变大 变宽。说明该实验设计的合理性与可应用性。 关键词：还原响应性 梳型嵌段聚合物 两亲性 胶束 释放 自组装 II II ABSTRACT In this paper, the polyglutamic acid polyethylene glycol amphiphilic block copolymer is synthesized by ring opening polymerization of methoxy-polyethylene glycol (PEG) as an initiator to the γ-propargyl-L-glutamic acid-N-urethane-protected carboxy anhydrides. We make use of methoxy-polyethylene glycol (PEG) to synthesize amino-methoxy-polyethylene glycol. Based on that product of amphiphilic block copolymer, the alkynyl of the glutamic acid segment is linked with disulfide-labeled reducing-responsive block polymer segment by the means of click. Meanwhile, we synthesize non-responsive one by the same method as a contrast. The final product is rodex-responsive and amphiphilic comb-like block polymer. In aqueous solutions, the polymer makes self-assembly to form degradable and amphiphilic polymer nano drug carrier micelles. These micelles with sensitivity are used to package, transport and release the cancer drugs. These micelles also have a higher stability and a better drug release. According to the concentration changing of reduced glutathione (GSH), the reducing-responsive micelles select the carried drug to control and release intelligently. In the experiment, the final synthetic material is characterized by HNMR, FT-IR and GPC. Through the PTI Fluorescence Master System, we have measured and calcul