主动靶向新生隐球菌的脂质体递药系统及其抗隐球菌肺脑合并感染的初步研究

发布时间：2018-03-08 01:18

本文选题：噬菌体展示　切入点：隐球菌病　出处：《药学学报》2016年07期 　论文类型：期刊论文

【摘要】：本文旨在构建一种能主动识别新生隐球菌的脂质体递药系统并探索其靶向治疗隐球菌病的可行性。以隐球菌菌体为靶物质,采用噬菌体随机12肽库筛选能特异性结合病原菌的功能多肽;进一步以该多肽为导向分子并通过偶联聚乙二醇-磷脂酰乙醇胺(PEG-DSPE)制备表面修饰多肽的脂质体,以体外真菌结合及体内荧光成像实验考察该脂质体的靶向性;在此基础上,以伊曲康唑为模型药物,制备载药脂质体并对其体外药效及体内抗隐球菌肺脑合并感染进行初步评价。结果表明,筛选所得多肽(序列为NNHREPPDHRTS)能特异性结合隐球菌,多肽修饰后的脂质体具有较好的体内外靶向性,其载药制剂粒径较小(88.25±2.43 nm)且分布均一,药物包封率高(88.05±0.25%)。经静脉给药后该制剂能有效清除肺部和脑部的病原菌,显著延长模型小鼠的生存时间,初步表现出靶向治疗隐球菌病的潜力,具有进一步研究价值并有望为抗真菌感染及新制剂研究提供有益的思路。
[Abstract]:The purpose of this paper is to construct a liposome delivery system which can recognize Cryptococcus neoformans actively and to explore the feasibility of its targeted therapy for Cryptococcus neoformans. The phage random 12 peptide library was used to screen the functional peptides which could specifically bind to the pathogen, and the liposomes were further prepared by coupling PEG-DSPE with PEG-DSPE. The in vitro fungal binding and in vivo fluorescence imaging were used to investigate the targeting of the liposome, and itraconazole was used as the model drug. The drug carrying liposome was prepared and its in vitro pharmacodynamics and anti-Cryptococcus pneumoencephalon co-infection were preliminarily evaluated. The results showed that the selected polypeptide (NNHREPPDHRTS) could specifically bind Cryptococcus to Cryptococcus. The polypeptide modified liposome had better targeting in vivo and in vitro, and the drug carrier was smaller than that of the drug carrier (88.25 卤2.43 nm). The drug encapsulation efficiency was higher than 88.05 卤0.25 nm. After intravenous administration, the drug could effectively clear the pathogenic bacteria in the lung and brain. The survival time of the model mice was significantly prolonged and the potential of targeted treatment of Cryptococcosis was initially demonstrated. It has further research value and is expected to provide useful ideas for the study of antifungal infection and new preparations.
【作者单位】：西南大学药学院;
【基金】：国家自然科学基金资助项目(21272187) 中央高校基本科研业务费(XDJK2015A012)
【分类号】：R943

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