本文選題：噬菌體展示　切入點(diǎn)：隱球菌病　出處：《藥學(xué)學(xué)報(bào)》2016年07期 　論文類型：期刊論文

【摘要】：本文旨在構(gòu)建一種能主動(dòng)識(shí)別新生隱球菌的脂質(zhì)體遞藥系統(tǒng)并探索其靶向治療隱球菌病的可行性。以隱球菌菌體為靶物質(zhì),采用噬菌體隨機(jī)12肽庫(kù)篩選能特異性結(jié)合病原菌的功能多肽;進(jìn)一步以該多肽為導(dǎo)向分子并通過偶聯(lián)聚乙二醇-磷脂酰乙醇胺(PEG-DSPE)制備表面修飾多肽的脂質(zhì)體,以體外真菌結(jié)合及體內(nèi)熒光成像實(shí)驗(yàn)考察該脂質(zhì)體的靶向性;在此基礎(chǔ)上,以伊曲康唑?yàn)槟Ｐ退幬?制備載藥脂質(zhì)體并對(duì)其體外藥效及體內(nèi)抗隱球菌肺腦合并感染進(jìn)行初步評(píng)價(jià)。結(jié)果表明,篩選所得多肽(序列為NNHREPPDHRTS)能特異性結(jié)合隱球菌,多肽修飾后的脂質(zhì)體具有較好的體內(nèi)外靶向性,其載藥制劑粒徑較小(88.25±2.43 nm)且分布均一,藥物包封率高(88.05±0.25%)。經(jīng)靜脈給藥后該制劑能有效清除肺部和腦部的病原菌,顯著延長(zhǎng)模型小鼠的生存時(shí)間,初步表現(xiàn)出靶向治療隱球菌病的潛力,具有進(jìn)一步研究?jī)r(jià)值并有望為抗真菌感染及新制劑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 鹵2.43 nm). The drug encapsulation efficiency was higher than 88.05 鹵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.
【作者單位】： 西南大學(xué)藥學(xué)院;
【基金】：國(guó)家自然科學(xué)基金資助項(xiàng)目(21272187) 中央高�；究蒲袠I(yè)務(wù)費(fèi)(XDJK2015A012)
【分類號(hào)】：R943

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