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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。
This article aims to construct a liposome delivery system that can actively identify Cryptococcus neoformans and explore its feasibility of targeting Cryptococcosis. Using Cryptococcus neoformans as a target substance, a random peptide library of phage was used to screen the functional polypeptide that specifically binds pathogenic bacteria. The polypeptide was further used as a targeting molecule and was prepared by conjugating with PEG-DSPE The liposomes with surface-modified peptides were tested for the targeting of the liposomes by in vitro fungal binding and in vivo fluorescence imaging. On the basis of this, the liposomes were prepared with itraconazole as a model drug and their liposomes were prepared In vitro drug efficacy and anti-cryptococcosis in vivo were initially evaluated. The results showed that the polypeptide obtained by screening (sequence NNHREPPDHRTS) could specifically bind to Cryptococcus, and the liposomes modified by the polypeptide had good targeting in vitro and in vivo. The particle size of the drug-loaded liposomes was small (88.25 ± 2.43 nm) and Uniform distribution, drug encapsulation efficiency (88.05 ± 0.25%). After intravenous administration, the preparation can effectively remove pathogens in the lung and brain, prolong the survival time of the model mice and initially display the potential of targeting the treatment of cryptococcosis, and has further research value and is expected to be anti-fungal infection and New formulation research provides useful ideas.