艾塞那肽聚乳酸-羟基乙酸共聚物纳米粒制备及体外评价

Preparation and in vitro evaluation of exenatide-loaded poly(lactic-co-glycolic acid) nanoparticles

目的:制备艾塞那肽聚乳酸-羟基乙酸共聚物[poly(lactic-co-glycolic acid),PLGA]纳米粒并对其进行体外评价及表征。方法:通过正交实验设计优化法筛选艾塞那肽PLGA纳米粒的处方及工艺,并通过动态光散射和透射电镜对其进行了表征,通过体外模拟胃肠液和Caco-2细胞模型对其稳定性和细胞摄取及转运进行评价。结果:通过正交设计最终确定了最佳处方工艺:内水相和油相的比例为1∶5,超声功率200 W,超声时间4 min,聚乙烯醇(polyvinyl alcohol,PVA)浓度为2%,初乳与外水相体积比为1∶20。所制得纳米粒粒径为116.2 nm,透射电镜显示PLGA纳米粒为类圆形球状纳米粒,表面规则。体外研究结果表明,PLGA纳米粒可延缓艾塞那肽在胃肠液中的释放,同时也明显增加了其稳定性(P<0.05),在人工胃液和人工肠液中孵育4 h后,仍分别有约50%和80%的保留。细胞实验表明,PLGA纳米粒的摄取和转运分别是对照组的7倍和5倍之多(P<0.05)。结论:PLGA纳米粒可作为艾塞那肽潜在的高效口服递药系统。

Objective:To prepare exenatide-loaded poly(lactic-co-glycolic acid)(PLGA)nanoparticles,and to evaluate its in vitro effect and characteristics.Methods:The orthogonal experimental design was used to screen out the optimal formulation and process of exenatide-loaded PLGA nanoparticles,and dynamic light.scattering and a transmission electron microscope were used for characterization.In vitro simulation of gastrointestinal fluid and Caco-2 cell model were used to evaluate its stability,cellular uptake,and cellular transport.Results:The optimal formulation and process were obtained by the orthogonal design,i.e.,a volume ratio of internal water phase to oil phase of 1:5,an ultrasonic power of 200W,an ultrasonic time of 4minutes,a concentration of polyvinyl alcohol of 2%,and a volume ratio of primary emulsion to external water phase of 1:20.The nanoparticles obtained had a diameter of 116.2nm and the transmission electron microscope showed that.PLGA nanoparticles had a sphere-like shape with a regular surface.The in vitro study demonstrated that PLGA nanoparticles significantly prolonged the release of exenatide in gastrointestinal fluid and improved its stability(P<0.05),and 50% of exenatide was retained after 4-hour culture in simulated gastric fluid,while 80% was retained after d-hour culture in simulated intestinal juice.The cell experiment showed that the uptake and transport of PLGA nanoparticles in the experimental group were 7 and 5 times those in the control group(P<0.05).Conclusion:PLGA nanoparticles may be a potential efficient oral drug delivery system for exenatide.