發(fā)布時(shí)間：2018-12-12 07:21

【摘要】：目的:探索阿苯達(dá)唑亞砜溫敏型原位凝膠(ABZSO/PLGA-PEG-PLGA)的殺蟲效果。方法:采用溶劑揮發(fā)法制備ABZSO/PLGA-PEG-PLGA,并考察了它的相變行為。通過傅里葉近紅外光譜分析、核磁共振對(duì)其進(jìn)行表征;采用無膜溶出法研究其體外釋藥規(guī)律。應(yīng)用Orign7.5考察了凝膠溶蝕與釋藥的關(guān)系和ABZSO/PLGA-PEG-PLGA的體外釋藥動(dòng)力學(xué);然后獲得了大鼠血漿中ABZSO/PLGA-PEG-PLGA的時(shí)藥曲線,并用DAS2.0對(duì)藥動(dòng)學(xué)參數(shù)進(jìn)行分析;通過研究ABZSO/PLGA-PEG-PLGA對(duì)秀麗隱桿線蟲的致死率來初步地探討其殺蟲效果;通過研究ABZSO/PLGA-PEG-PLGA體內(nèi)、外抗泡球蚴效果進(jìn)一步驗(yàn)證其殺蟲效果。首先,應(yīng)用ABZSO/PLGA-PEG-PLGA處理體外培養(yǎng)泡球蚴并統(tǒng)計(jì)原頭節(jié)的存活率,然后,采用掃描電鏡(SME)觀察各處理組泡球蚴或原頭節(jié)形態(tài)變化;而體內(nèi)實(shí)驗(yàn)則以各藥物組治療泡球蚴病大鼠動(dòng)物模型后通過檢查泡球蚴體積大小來判斷其抗泡球蚴的效果。結(jié)果:結(jié)果顯示本實(shí)驗(yàn)所制ABZSO/PLGA-PEG-PLGA在25℃時(shí)為透明、均勻的溶液,且能順利通過25G針頭,并展示了ABZSO/PLGA-PEG-PLGA的凝膠狀態(tài)和沉淀狀態(tài),此外,相變溫度結(jié)果顯示其膠凝溫度為30℃,沉淀溫度為37℃;紅外光譜和核磁共振圖譜均顯示ABZSO與PLGA-PEG-PLGA的結(jié)構(gòu)未發(fā)生改變;體外釋放曲線結(jié)果顯示ABZSO/PLGA-PEG-PLGA在第6天時(shí)ABZSO累積釋放量?jī)H為80.3%,且體外釋藥與凝膠的溶蝕成線性關(guān)系(R~2=0.0.999),而體外釋放動(dòng)力學(xué)結(jié)果表明,ABZSO/PLGA-PEG-PLGA的釋放符合Higuchi方程(R~2=0.992);藥動(dòng)學(xué)研究表明ABZSO/PLGA-PEG-PLGA組Cma x(178.09 ng/ml)高于ABZSO普通制劑組(131.98 ng/ml);ABZSO/PLGA-PEG-PLGA殺蟲效果的初步考察實(shí)驗(yàn)表明ABZSO/PLGA-PEGPLGA組對(duì)秀麗隱桿線蟲的致死率顯著高于ABZSO普通制劑組。通過對(duì)ABZSO/PLGA-PEG-PLGA體內(nèi)外抗泡球蚴的考察進(jìn)一步研究其殺蟲效果。藥物處理體外培養(yǎng)泡球蚴18d時(shí),ABZSO/PLGA-PEG-PLGA(40μg/ml)組原頭節(jié)存活率顯著低于ABZSO(40μg/ml)組;掃描電鏡結(jié)果顯示ABZSO/PLGA-PEG-PLGA(80μg/ml)組的原頭節(jié)結(jié)構(gòu)被嚴(yán)重破壞;動(dòng)物體內(nèi)實(shí)驗(yàn)表明ABZSO/PLGA-PEG-PLGA(4mg/ml)組對(duì)抗泡球蚴效果優(yōu)于其他各藥物組。因此,ABZSO/PLGA-PEG-PLGA的抗泡球蚴效果顯著。結(jié)論:本文成功制備了可注射用制劑-阿苯達(dá)唑亞砜溫敏型原位凝膠且已被證明ABZSO成功載入PLGA-PEG-PLGA且各自的結(jié)構(gòu)未發(fā)生改變;藥動(dòng)學(xué)、藥效學(xué)的實(shí)驗(yàn)研究表明ABZSO/PLGA-PEG-PLGA是一種顯著優(yōu)于ABZSO普通制劑的緩釋制劑且對(duì)秀麗隱桿線蟲具有殺蟲效果;此外,體內(nèi)外抗泡球蚴的實(shí)驗(yàn)結(jié)果進(jìn)一步證實(shí)了ABZSO/PLGA-PEG-PLGA具有顯著的殺蟲效果。
[Abstract]:Objective: to investigate the insecticidal effect of albendazole sulfoxide in situ gel (ABZSO/PLGA-PEG-PLGA). Methods: ABZSO/PLGA-PEG-PLGA, was prepared by solvent volatilization method and its phase change behavior was investigated. Fourier transform near infrared spectroscopy (FNIR) and nuclear magnetic resonance (NMR) were used to characterize the drug release in vitro. The relationship between gel dissolution and drug release and the in vitro release kinetics of ABZSO/PLGA-PEG-PLGA were investigated by Orign7.5, then the time curve of ABZSO/PLGA-PEG-PLGA in rat plasma was obtained and the pharmacokinetic parameters were analyzed by DAS2.0. The killing effect of ABZSO/PLGA-PEG-PLGA was preliminarily studied by studying the mortality of ABZSO/PLGA-PEG-PLGA to nematodes, and the efficacy of ABZSO/PLGA-PEG-PLGA was further verified by studying the effect of anti-alveolar hydatid in vivo and in vitro. Firstly, ABZSO/PLGA-PEG-PLGA was used to treat alveolar hydatid in vitro and the survival rate of primordial ganglia was counted. Then the morphological changes of alveolar hydatid or proto-cephalus were observed by scanning electron microscope (SME). In vivo, the antialveolar echinococcal effect was evaluated by examining the volume of alveolar hydatid in different drug groups after treating the rat model of alveolar echinococcosis. Results: the results showed that the ABZSO/PLGA-PEG-PLGA prepared in this experiment was transparent and uniform solution at 25 鈩，

本文編號(hào)：2374173