PCL/PEO药物缓释体系在多级熔融拉伸口模中的形态调控及其对药物释放行为的影响

Many polymers and their composites have been used as the carriers for the controlled release of drugs, by virtue of a series of advantages, including biocompatibility, biodegradability, absence of toxicity and excellent mechanical property. The investigation of the morphology and structure variation of polymer matrix during melting preparation is profound and significant to achieve demanding requirements for different drug release systems. In this research proposal, the melting blend of polycaprolactone (PCL) and polyethylene oxide (PEO) will be fabricated through multistage stretching extrusion technology. The dispersed phase morphology of PEO will be adjusted flexibly through the processing variation of multistage stretching extrusion, as well as the designing of structure of polymers and drugs. As a result, the release of drugs with different solubility and effect can be easily controlled, in the aim of achieving demanding requirements for different drug release systems. In order to obtain controlled release of drugs, compositional parameters will be investigated, including the molecular weight of PEO, weight ratio of PEO to PCL, morphology structure of PEO and PCL, the drug loading and dispersion, and the interaction of polymers and drugs. The mechanism of polymer degradation and drug release was determined, and the drug release kinetics of composite release systems prepared through multistage stretching extrusion was established, based on the modification of traditional drug release mechanism. The completion of the research will provide a new thought for designing and preparing composite drug release materials with high flexibility to achieve demanding requirements for different drug release systems, and play a very significant role in both academic and industrial fields.

本项目拟针对传统熔融法制备药物缓释体系给药方案难以灵活调控、不同药效和释放行为难以较好复配等缺点，采用聚ε-己内酯(PCL)为基体，聚氧化乙烯(PEO)为分散相，通过课题组自行设计的多级微拉伸挤出系统制备PCL/PEO复合药物缓释体系。调节多级微拉伸挤出参数(如拉伸级数、温度等)，获得分散相形态分别为球形、纤维状和片状的载药体系，建立分散相形态结构与药物释放的关系，丰富药物释放理论模型。设计药物和聚合物结构使药物选择性分散于基体或分散相，也可使不同药效药物分别负载于基体和分散相，实现两种药物的复配释放，满足药物缓释体系的不同释药需求。研究分散相含量及形态结构、聚合物降解行为、药物分布及含量等参数对药物释放行为的影响，揭示其生物降解和药物缓释规律，建立不同形态结构复合药物载体的药物释放和生物降解动力学模型，为新型生物降解高分子基药物缓释材料的构筑提供理论依据，具有重要的理论意义和应用前景。

本项目针对传统熔融法制备药物缓释体系给药方案难以灵活调控、不同药效和释放行为难以较好复配等缺点，采用聚ε-己内酯(PCL)为基体，选择水溶性不同的模型药物制备PCL基载药体系，首先研究药物与PCL的相互作用对药物在PCL基体中的形态结构及其释药行为的影响，并研究加工工艺对药物在基体中的形态结构及释药行为的影响，对其药物释放机理进行分析；在此基础上，以水溶性不同的生物降解材料聚氧化乙烯(PEO)和月桂酸（LA）为分散相，采用熔融挤出加工工艺对分散相和药物形态结构进行调控，建立分散相形态结构与药物释放的关系，研究分散相含量及形态结构、聚合物降解行为、药物含量等参数对药物释放行为的影响，揭示其生物降解和药物缓释规律，建立不同形态结构复合药物载体的药物释放和生物降解动力学模型，为新型生物降解高分子基药物缓释材料的构筑提供理论依据，具有重要的理论意义和应用前景。