金属离子诱导功能性超支化聚合物的自组装及其对药物的可控释放

Hyperbranched polymers with nanovoid structures is a promising generation of nano-carriers for drugs. The preparation of both amphiphilic hyperbranched polymers (HBPs) as assembly units and organometallic coordination polymers as drug carriers involves complex and tedious synthetic processes, therefore, investigations on the self-assembly of non-amphiphilic HBPs prepared by one-step technology and on its controlled release for drugs are important for wide application of HBPs. In this work, hybrid nanoparticulates with controllable morphology and size will be fabricated through metal-mediated self-assembly of functional (carboxyl, hydroxyl, amino etc.). Hyperbranched polymers, and their drug realease behavior are also researched. Interaction between metal ions, HBPs and drugs, drived force for self-assembly, crystal behavior and self-assembly mechanism will be anaylized by DSC, XPS, XRD and NMR techniques. We will also discuss the controllabilities and effects of morphology, size and crystalline about HBPs self-assemblies on loaded capacity and release property of drugs. Through above research, novel self-assemblies of functional HBPs with controllable morphology and size, which can loaded capacity and release performance of drugs, will be obtained as well as a novel self-assembly mechanism of functional HBPs induced by metal ions, crystal and fractal mechanism. In addition, a novel drug delivery carrier as well as relative theory and technology will be obtained.

具有纳米空腔结构的超支化聚合物是药物可控释放的新一代纳米载体,作为组装基元的两亲性超支化聚合物和作为药物载体的金属有机配位聚合物的制备工艺均较繁琐，探索一步法制备的非两亲性超支化聚合物的自组装及其药物可控释放载体的研究对其应用具有重要意义。本项目拟研究金属离子诱导功能性（羧基、羟基、氨基等）超支化聚合物制备形貌和尺寸可控的自组装体及其对药物的控制释放性能。以XPS、XRD、NMR、DSC等技术对金属离子与超支化聚合物以及药物之间的结合方式、组装驱动力、结晶行为进行分析和表征,探索自组装机理；研究自组装体形貌、尺寸和结晶性对其载药量、药物缓释性能的影响及其可控性。通过上述研究，将获得金属离子配位诱导驱动功能性超支化聚合物的杂化自组装机理、相分离过程特征、结晶和分形机理，获得形貌、尺寸、载药量和缓释性能可控的功能性超支化聚合物自组装体，可望获得新型的药物控制释放载体及相关技术和理论。

超支化聚合物自组装获得胶束、囊泡、薄膜等超分子结构在药物载体、基因载体、催化剂等领域具有潜在的应用而成为目前高分子界研究的热点。超支化聚合物自组装研究基元主要以制备工艺繁琐的RAFT和接枝改性的嵌段型超支化聚合物为主，由其制备的自组装体大多为无定型结构，耐热性和稳定性偏弱，应用难以扩展，而一步法合成的功能端基超支化聚合物不具备两亲性性质难于直接自组装。研究新型自组装基元、结构稳定性优异的自组装体是超支化自组装领域的重要挑战。本项目采用金属（铜、铁）离子和氢键相互作用诱导功能端基超支化聚合物自组装，获得了具有结晶和分形行为的雪花状、环形和球晶等多种自组装体。详细研究了影响自组装体形貌和尺寸的各种因素，包括溶液浓度、温度、溶剂和湿度等，并利用FT-IR、XPS、XRD等技术分析了金属离子和聚合物之间的结合方式。通过分形维数的计算，分析自组装体的分形行为。结合组装形貌的生长过程和扩散限制聚集模型理论（DLA），提出了组装机理。由于金属离子与设计制备的超支化聚合物和抗癌药物同时键接的能力弱，因此需要进一步优化超支化聚合物的结构。通过一步法制备了以可降解超支化聚（ε-己内酯）为核的两亲性超支化聚合物。这种两亲性聚合物在水溶液中能自组装成胶束。我们对胶束的尺寸、形貌、载药能力、体外释药行为和体外细胞毒性进行了研究。