丹参酮Ⅱ重组高密度脂蛋白载药系统的构建

项目名称： 丹参酮Ⅱ重组高密度脂蛋白载药系统的构建

项目编号： No.81072587

项目类型： 面上项目

立项/批准年度： 2011

项目学科： 金属学与金属工艺

项目作者： 刘建平

作者单位： 中国药科大学

项目金额： 10万元

中文摘要： 根据高密度脂蛋白（HDL）体内独特的巡行与代谢路线、逆向转运胆固醇作用以及抗动脉粥样硬化和血管保护功能等生物学特性，将HDL的组成成份进行重组和优化，作为一种新型的载药系统，用来包载治疗心血管疾病的药物丹参酮Ⅱ，期待在体内具有更好的向血管壁粥样硬化病灶区域传输的特性及治疗作用。本课题组将对这种药物－新载体复合系统的制剂学、生物药剂学、药动学和药效学等进行研究与完善，内容涉及载体构造及载体从新生态向成熟态的变构动力学考察，制剂处方和工艺的筛选、调整与优化，动物体内的组织分布和趋靶性（血管壁新靶点）测评，药动学及药效学试验等。 本项目研究的成果将为进一步了解重组高密度脂蛋白作为新型载药系统的运作价值，拓展其血管壁新靶区，以及优化载体结构等关键问题的解决，提供详实有力的科学试验方法与数据。

中文关键词： 脂质体；纳米粒；重组高密度脂蛋白；靶点；丹参酮Ⅱ

英文摘要： The present work will concern the development of reconstituted high density lipoprotein (rHDL) to serve as a novel delivery vehicle for cardiovascular drug like Tanshinone Ⅱ due to the attractive attributes of HDL including unique circulating route and metabolic pathway, the function in reverse cholesterol transport, in the prevention or reversal of atherosclerosis and in blood vessel protection. This optimized rHDL are expected to exert a better effect on drug delivery to atherosclerotic lesions on vascular wall as well as therapeutic effect. In this subject, the reconstituted drug-HDL complex will be prepared and studied from several aspects such as pharmaceutics, biopharmaceutics, pharmacokinetics (PK), pharmacodynamics (PD) and so on. The contents refer to morphology and structure of carrier, kinetics of morphological change of drug-HDL complex from nascent to mature state, selection and optimization of formulation and preparation technique, investigation and evaluation of tissue distribution in animals and new target effect for vascular wall, PK and PD experiments. This subject would be an exploration to develop HDL as a novel drug delivery system, discover its new target point on vascular wall and optimize the structure of carrier. It will provide full and accurate scientific test method and data.

英文关键词： liposomes; nanoparticles; reconstituted high density lipoprotein; target point; Tanshinone Ⅱ