配体修饰的双功能耐药菌靶向脂质体的构建及其细胞内化机制

项目名称： 配体修饰的双功能耐药菌靶向脂质体的构建及其细胞内化机制

项目编号： No.81202488

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 药物学、药理学

项目作者： 李桂玲

作者单位： 中国医学科学院医药生物技术研究所

项目金额： 23万元

中文摘要： 细菌耐药性问题已成为日益严峻的全球性问题，全新结构和新作用机制的抗菌活性药物研究周期长、成本高，因此，整个药学领域都在寻找更为迅速而高效的解决策略。对具有抗菌活性的给药系统研究正渐趋成为国际药学领域一个研究热点。在大量的文献调研和前期研究工作基础上，本项目拟选择穿膜肽和麦胚凝集素为配体，将其分别化学偶联至脂质膜材表面，利用穿膜肽的细胞膜穿透特性，以及凝集素的细菌细胞壁靶向特性，构建出一种双功能、具有耐药菌靶向特性的脂质体给药系统，对其体内外性质、靶向性和抗耐药性进行研究，并初步探讨其可能的耐药菌细胞内化作用机制。在穿膜肽用于抗耐药菌给药系统的研究，以及凝集素用于细菌靶向性给药系统的研究方面，国内外仅有少量的文献报道；而对于二种配体联合应用构建的双功能给药系统，尚无任何文献报道。因此，本项目的研究结果有望为耐药菌感染的治疗提供一种具有较强创新性和良好应用前景的给药系统。

中文关键词： 耐甲氧西林金黄色葡萄球菌；靶向；细菌生物膜；抗耐药策略；巨噬细胞

英文摘要： Antibiotic-resistance has become a deteriorating global problem, as the development of antibiotics with novel structures and new antimicrobial mechanisms is time-consuming and expensive; therefore, the whole pharmaceutical society is seeking for faster and more effective strategies. Under this background, the study of antimicrobial drug delivery systems is becoming a hot topic in the international pharmaceutical research. Based on extensive literature review and previous study, this project aims to couple cell-penetrating peptide (CPP) and wheat germ agglutinin (WGA) as the targeting ligands to the surface of liposomes; the CPP's membrane-penetrating ability and WGA's cell wall binding specificity are used for building a bi-functional and antibiotic-resistant bacteria targeting liposomal drug delivery system, which will be characterized in vitro/in vivo and will be preliminarily studied with respect to its targeting, anti-drug resistance as well as possible internalization mechanism for drug-resistant bacteria cells. By far only a small number of papers were published in the field of applying CPP to drug delivery systems for antibiotic-resistant bacteria and in the field of using WGA for bacteria-targeting drug delivery systems; while combining these two ligands for building a bi-functional drug delivery system

英文关键词： Methicillin-resistant Staphylococcus aureus；Targeting；Bacterial biofilm；Anti-resistant strategy；Macrophages