阿苯达唑亚砜温敏型原位凝胶制备及杀虫效果研究

发布时间：2018-12-12 07:21

【摘要】：目的:探索阿苯达唑亚砜温敏型原位凝胶(ABZSO/PLGA-PEG-PLGA)的杀虫效果。方法:采用溶剂挥发法制备ABZSO/PLGA-PEG-PLGA,并考察了它的相变行为。通过傅里叶近红外光谱分析、核磁共振对其进行表征;采用无膜溶出法研究其体外释药规律。应用Orign7.5考察了凝胶溶蚀与释药的关系和ABZSO/PLGA-PEG-PLGA的体外释药动力学;然后获得了大鼠血浆中ABZSO/PLGA-PEG-PLGA的时药曲线,并用DAS2.0对药动学参数进行分析;通过研究ABZSO/PLGA-PEG-PLGA对秀丽隐杆线虫的致死率来初步地探讨其杀虫效果;通过研究ABZSO/PLGA-PEG-PLGA体内、外抗泡球蚴效果进一步验证其杀虫效果。首先,应用ABZSO/PLGA-PEG-PLGA处理体外培养泡球蚴并统计原头节的存活率,然后,采用扫描电镜(SME)观察各处理组泡球蚴或原头节形态变化;而体内实验则以各药物组治疗泡球蚴病大鼠动物模型后通过检查泡球蚴体积大小来判断其抗泡球蚴的效果。结果:结果显示本实验所制ABZSO/PLGA-PEG-PLGA在25℃时为透明、均匀的溶液,且能顺利通过25G针头,并展示了ABZSO/PLGA-PEG-PLGA的凝胶状态和沉淀状态,此外,相变温度结果显示其胶凝温度为30℃,沉淀温度为37℃;红外光谱和核磁共振图谱均显示ABZSO与PLGA-PEG-PLGA的结构未发生改变;体外释放曲线结果显示ABZSO/PLGA-PEG-PLGA在第6天时ABZSO累积释放量仅为80.3%,且体外释药与凝胶的溶蚀成线性关系(R~2=0.0.999),而体外释放动力学结果表明,ABZSO/PLGA-PEG-PLGA的释放符合Higuchi方程(R~2=0.992);药动学研究表明ABZSO/PLGA-PEG-PLGA组Cma x(178.09 ng/ml)高于ABZSO普通制剂组(131.98 ng/ml);ABZSO/PLGA-PEG-PLGA杀虫效果的初步考察实验表明ABZSO/PLGA-PEGPLGA组对秀丽隐杆线虫的致死率显著高于ABZSO普通制剂组。通过对ABZSO/PLGA-PEG-PLGA体内外抗泡球蚴的考察进一步研究其杀虫效果。药物处理体外培养泡球蚴18d时,ABZSO/PLGA-PEG-PLGA(40μg/ml)组原头节存活率显著低于ABZSO(40μg/ml)组;扫描电镜结果显示ABZSO/PLGA-PEG-PLGA(80μg/ml)组的原头节结构被严重破坏;动物体内实验表明ABZSO/PLGA-PEG-PLGA(4mg/ml)组对抗泡球蚴效果优于其他各药物组。因此,ABZSO/PLGA-PEG-PLGA的抗泡球蚴效果显著。结论:本文成功制备了可注射用制剂-阿苯达唑亚砜温敏型原位凝胶且已被证明ABZSO成功载入PLGA-PEG-PLGA且各自的结构未发生改变;药动学、药效学的实验研究表明ABZSO/PLGA-PEG-PLGA是一种显著优于ABZSO普通制剂的缓释制剂且对秀丽隐杆线虫具有杀虫效果;此外,体内外抗泡球蚴的实验结果进一步证实了ABZSO/PLGA-PEG-PLGA具有显著的杀虫效果。
[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，

本文编号：2374173