海藻酸钠-石墨烯基结肠靶向给药系统构建及门脉联控化疗机制研究

项目名称： 海藻酸钠-石墨烯基结肠靶向给药系统构建及门脉联控化疗机制研究

项目编号： No.21476052

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 有机化学

项目作者： 蔡祥

作者单位： 广东省结核病控制中心

项目金额： 88万元

中文摘要： 结肠癌术后癌细胞易肝转移，结肠靶向缓释给药系统有望解决常规肝门静脉置管化疗的诸多技术难题，但目前存在释药速率无法有效控制、定位不精确、易受微环境影响和稳定性差等问题。本项目通过在海藻酸钠修饰石墨烯载体上负载化疗药物，构建新型海藻酸钠-石墨烯基结肠靶向给药系统，具有结肠定位粘附、安全性高、肝门静脉释药速率可联控和载药量大等特点。系统研究氧化石墨烯、丁二胺接枝海藻酸钠和化疗药物的组成结构，交联、还原及载药工艺对载体及其给药系统的组成、结构和形态的影响规律，获得结构可控的载体及其给药系统；进一步研究给药系统的组成结构与其理化性能、靶向性、粘附性、生物毒性、门脉联控性及对结肠癌肝转移抑制作用的内在关系，揭示给药系统的门脉联控化疗机制，构建动物模型，建立对结肠癌肝转移有明显抑制作用的结肠靶向给药系统。该研究成果有利于提高我国结肠靶向给药系统的基础研究水平，为结肠癌肝转移的治疗提供新途径和思路。

中文关键词： 石墨烯；给药系统；构建；门脉联控；化疗机制

英文摘要： The cancer cell is easily spread to liver after the operation treatment of colon cancer. The colon-specific sustained-release drug delivery system is expected to solve many technical problems of conventional hepatic portal venous catheter chemotherapy. However, many problems are currently existed, such as the poorly effective control of release rate, inaccuracy of positioning, easy influence by microenvironment and poor stability. In this project, we construct a new type of colon-specific drug delivery system based on sodium alginate-graphene by loading the chemotherapy drug on the carrier of sodium alginate-modified graphene, which has characteristics like positioning adhesion of colon, high safety, joint control of drug release rate of hepatic portal vein, high capacity of drug loading, etc. Moreover, the compositional structure among graphene oxide, butanediamine-grafted sodium alginate and chemotherapy drug and the influence rule of cross-linking, reduction and drug-loading process on the compositions, structures and morphologies of carrier and drug delivery system are studied systematically to obtain the carrier and drug delivery system with controllable structures; Furthermore, the inner relationship between composition and structure of drug delivery system and its physical and chemical property, colon targeting, adhesion, biological toxicity, portal vein-joint controlled release and inhibition effect on colon cancer spread to liver is also studied to clarify the mechanism of portal vein-joint controlled chemotherapy of drug delivery system; then, based on the research of the constructed of animal models, a jointly controlled drug delivery system which owns obvious inhibition effect on colon cancer spread to liver was established. The result of this study is helpful to improve the basic research level of our colon-specific sustained-release drug delivery system, and offers a new approach and idea for the treatment of colon cancer spread to liver.

英文关键词： graphene;drug delivery system;construction;portal vein jointly controlled;chemotherapy mechanism