聚己内酯/多孔镁复合材料的载药和控释机制研究

Biodegradable magnesium (Mg) and its alloy is an important kind of biomedical materials. The mechanical properties of porous magnesium are close to human physiological hard tissue, its porous structure is beneficial to the growth of physiological tissue and its pores can provide carrier for compositing other substances. Therefore, porous Mg has important application prospects in the orthopedic repair material and drug delivery. Based on porous Mg as matrix, the current project is proposed. First, a biodegradable polycaprolactone (PCL) is adopted as coating content and a kind of PCL/porous magnesium composite is obtained. Second, two kinds of different drug-loaded composites are obtained by direct method of drug-dispersal and indirect method of drug-encapsulation in pH-responsive nanocontainer. Third, the degradable properties of composite in vitro and in vivo are studied systermly and the interaction relationship among the porous Mg, PCL, and drug-loaded pH-responsive nanocontainer are synthetically analysized. Furthermore, the effect of the degradation process and the two different drug-loading methods on the drug release of composite are deeply investigated. In the end, the load and controlled-release mechanism of drugs are revealed. The corresponding results will provide important theoretical basis on the development of new biodegradable magnesium-based composites for controlled drug release.

可生物降解镁及镁合金是一种重要的生物医用材料。多孔镁的力学性能与人体生理硬组织相近，多孔结构有利于生理组织的生长，孔隙能够作为载体复合其它物质，在新型骨科修复材料和药物负载方面具有重要的应用前景。本项目以多孔镁为基体，拟开展如下研究。首先，以可生物降解的聚己内酯为涂层组分，制备聚己内酯/多孔镁复合材料。其次，通过直接的分散技术和间接的pH响应型纳米容器封装技术，获得两类载药复合材料。进一步，系统研究复合材料的体内外降解性能和影响规律，综合分析多孔镁、聚己内酯和载药纳米容器间的作用关系。在此基础上，深入探索复合材料的降解行为、直接和间接载药法对药物释放的影响规律。最后，揭示聚己内酯/多孔镁复合材料的药物负载和可控释放机制。相关研究结果将为发展新型可控释药的生物降解镁基复合材料提供重要的理论依据。

本项目以多孔镁为基体（孔隙率：0~40%），开展了深入研究。首先，利用层层自组装技术，在中空介孔二氧化硅纳米颗粒的表面交替沉积海藻酸钠与壳聚糖，构建了pH和镁离子双重刺激响应型的纳米载药体，该载药体能有效包载药物，例如对抗生素盐酸万古霉素的载药率和包封率分别达到13.52%和82.47%。进一步，以聚多巴胺作为粘附层将多孔镁与纳米载药体复合，制备了多孔镁/纳米载药体复合材料。在此基础上，系统研究了该复合材料的药物负载、控制释放、降解行为、抗菌能力和生物相容性，综合分析了多孔镁基体与聚多巴胺及纳米载药体之间的作用关系。研究结果表明，该体系的药物负载随多孔镁孔隙率的增大而增加，且呈现出由金属镁自身腐蚀降解而触发的pH和镁离子协同双重刺激响应的药物释放规律。这种创新性的金属镁自触发药物控制释放平台的成功搭建标志着预期研究目标的顺利实现，具有重要的科学意义。而且相关研究结果的取得为发展镁基功能新材料提供了必要的理论依据，在新型骨科修复等生物医用材料领域呈现出广阔的应用前景。