基于超分子聚合物前药的可注射载药水凝胶-高分子化学与物理专业论文.docxVIP

优秀毕业论文 精品参考文献资料 摘要摘要 摘要 摘要 近年来在药物控释研究领域中，环境敏感聚合物得到了广泛的关注及应用，通过将抗 肿瘤药物以可降解共价键修饰于环境敏感聚合物分子链上制备聚合物前药，大大提高药物 的稳定性并实现其可控释放。然而，聚合物均存在分子量分布且分子量不明确，难以通过 FDA审批进入临床应用。本课题基于主客体作用设计了一种pH敏感的超分子聚合物前药。 选用金刚烷与B一环糊精这对稳定的主客体作用力作为结合点实现金刚烷改性的小分子前 药和环糊精聚合物的稳固连接，很好地综合小分子前药的高纯度特点和环糊精聚合物的高 稳定性优势。 通过苯甲亚胺键将阿霉素修饰于对醛基苯甲酸金刚烷甲酯从而制备酸响应的小分子 前药，分别制备两类可注射载药水凝胶体系。一类是通过天然大分子葡聚糖氧化改性用以 接枝环糊精，小分子前药通过金刚烷与环糊精的主客体作用载到葡聚糖主链上形成超分子 聚合物前药，通过水溶性羧甲基壳聚糖原位交联形成可注射载药水凝胶。另一类采用胺化 环糊精与聚乙二醇二丙烯酸酯的迈克尔加成反应制备末端为双键的环糊精树枝状聚合物， 通过环糊精和金刚烷间的主客体作用，合成超分子聚合物前药；最后通过多巯基聚乙二醇 聚合物原位交联形成可注射载药水凝胶。 实验结果表明，具有酸响应性的可注射水凝胶可在肿瘤部位局部给药，并实现持续刺 激响应性药物释放。凝胶具备良好的生物相容性及生物降解性，有望作为一种临床应用的 局部给药系统。 关键词：可注射水凝胶，pH响应，超分子前药，席夫碱反应，巯一烯“点击”反应 万方数据 AbstractAbstract Abstract Abstract Recently,environmentally sensitive polymers have been widely studied and applied in the materials for drug controlled release．Antitumor drugs have been covalently bonded onto the environmentally sensitive polymers to form polymeric prodrugs in order to improve the stability of the drugs and achieve the controlled release of the drugs．However,because all polymers have polydispersity,these covalently bonded polymeric prodrugs not pure chemical compounds，but mixtures，which make it difficult for them to be approved by the drug administration of most countries．Herein，we developed a novel pH·sensitive supramolecular polymeric drug based on host-guest interaction．Adamantane modified small molecular prodrug was firmly connected to the cyclodextrin polymer to form a supramolecular polymeric drug through the strong host-guest interaction between p-cyclodextrin and adamantane moieties， which could combine the advantages of polymeric prodrug and purity of the small molecular prodrug． An acid．sensitive small molecular prodrug，adamantane-modified doxorubicin(AD—DOX)， was synthesized via an acid．1abile benzoic—imine linkage between adamantine benzaldehyde and doxorubicin．We developed two injectable drug—loaded hydrogels．On one hand，13-cyclodextrin modified polyaldehyde dextran(PAD—CD)，was synthesize