两新性嵌段共聚物胶束作是为药物载体的分析.docxVIP

摘要摘要 摘要 摘要 两亲性嵌段共聚物通过在水溶液中的自组装行为，形成具有核壳结构的聚 合物胶束，可将疏水性药物包裹入核内作为药物载体，具有增大药物利用率、 提高靶向性、降低副作用等特点，展现出广泛的应用前景。本文基于嵌段共聚 物与药物之间的疏水作用／离子作用多重协同作用原理，设计并制备了系列聚合 物胶束，对聚合物载药胶束的负载能力、释放性能以及靶向作用等进行了研究。 主要内容包括： 1．以聚乙二醇为亲水链段，引发单体甲基丙烯酸正丁酯(nBMA)和甲基丙 烯酸叔丁酯(tBMA)聚合，用三氟乙酸脱除叔丁基后，使聚合物中既包含疏水 基团又包含一定量的羧酸基团。利用疏水基团与药物阿霉素的疏水作用，以及 羧酸负离子与阿霉素氨基正离子间的离子作用，将药物包裹形成具有核壳结构 的载药胶束。 2．通过调节聚合物链段中羧基的含量，调节疏水作用与离子作用的比例，研 究胶束对药物的负载量、负载效率、体外环境释药性能以及pn响应性的变化。 实验结果表明羧基含量越高胶束对pH值变化越敏感，但载药性能则是在一定的 羧基比例范围内最高。 3．引入末端接有叶酸的嵌段共聚物链段，混合制备复合载药胶束，使胶束表 面接有叶酸基团，作为肿瘤组织表面叶酸受体的识别基团，为胶束提供叶酸靶 向功能。通过流式细胞实验、激光共聚焦实验和细胞毒性实验，比较含有叶酸 受体识别基团的载药胶束与普通胶束、自由药物差别，研究载药胶束的靶向性 能。研究表明，接有叶酸识别受体的聚合物载药胶束能显著增加对肿瘤细胞的 识别能力，进入细胞速度加快，对细胞的毒性也比无叶酸的胶束高。 关键词：嵌段共聚物胶束阿霉素协同作用药物释放叶酸靶向 AbstractAbstract Abstract Abstract n is well known that the amphiphilic block copolymers assemble together to micelles when tlley dissolve in a selective solvent，forming core-shell stmcture．This kind of s仃ucture can be used as a drug delivery system by entrapping drug into the core．111e drug—loaded micelles have longevity in blood circulation,less side-effects，high drug loading capacity and target·specific．In this paper,doxombicin(DOX)-loaded micelles were prepared by dialysis method as drug carriers．And micelles Were researched on loading capacity,drug release and target-specific．The contents of the corresponding research works are shown as follows． 1．Synthesized the block copolymers by using PEG macromolecular initiator with nBMA and tBMA．The segments of tBMA was changing to MAA by using trifluoroacetic acid．So there were hydrophobic segment and carboxyl group in block copolymers．DOX was loaded into the core of micelles through combined action of ionic bond between MAA and DOX,and hydrophobic interaction． 2．Adjusted the synergy interaction composed of ionic bond and hydrophobic interaction by changing the ratio of MAA in block polymer．11lc drug-loading capacity／efficiency and drug release behavior in vivo Was studied．It shows that the ability of pH response Was as stronger aS more c