Singh Gurinder, Pai Roopa S
Department of Pharmaceutics, Faculty of Pharmacy, Al-Ameen College of Pharmacy , Bangalore, Karnataka , India.
Drug Deliv. 2014 Dec;21(8):627-35. doi: 10.3109/10717544.2013.867382. Epub 2013 Dec 18.
The objective of this study was to develop systematically optimized (OPT) nanoparticles (NPs) providing a controlled release using PLGA of emtricitabine (FTC) employing Formulation by Design (FbD), and evaluate their in vitro and in vivo performance. FTC generates severe adverse effects with risks of toxicity. Thus, NPs were prepared to reduce these drawbacks in this study. The NPs were prepared by water-in-oil-in-water (w/o/w) emulsion method, followed by high-pressure homogenization. The FTC NPs were systematically OPT using 3(2) central composite design and the OPT formulation located using overlay plot. The pharmacokinetics and in vivo biodistribution of OPT-FTC NPs were investigated in male Wistar rats via the oral administration. Transmission electron microscopy studies on OPT-FTC NPs demonstrated uniform shape and size of particles. In vitro release was sustained up to 15 days in PBS pH 7.4. Augmentation in the values of Cmax (1.63 fold) and AUC0-∞ (5.39 fold) indicated significant enhancement in the rate and extent of bioavailability by the OPT-FTC NPs compared to pure drug. OPT-FTC NPs showed 2.325 fold increase in the values of FTC concentrations in liver. The OPT-FTC NPs was found to be quite stable during 6 months of study period. Hence, the developed OPT-FTC NPs can be used as drug carrier for sustained/prolonged drug release and/or to reduce toxic effects.
本研究的目的是采用设计处方（FbD），利用聚乳酸-羟基乙酸共聚物（PLGA）开发系统优化（OPT）纳米颗粒（NPs），以实现恩曲他滨（FTC）的控释，并评估其体外和体内性能。FTC会产生严重的不良反应并有中毒风险。因此，本研究制备了纳米颗粒以减少这些缺点。纳米颗粒通过水包油包水（w/o/w）乳液法制备，随后进行高压均质处理。使用3（2）中心复合设计对FTC纳米颗粒进行系统优化，并使用叠加图确定优化配方。通过口服给药，在雄性Wistar大鼠中研究了OPT-FTC纳米颗粒的药代动力学和体内生物分布。对OPT-FTC纳米颗粒的透射电子显微镜研究表明颗粒形状和尺寸均匀。在pH 7.4的磷酸盐缓冲液（PBS）中，体外释放可持续15天。与纯药物相比，OPT-FTC纳米颗粒的Cmax值（1.63倍）和AUC0-∞值（5.39倍）增加，表明生物利用度的速率和程度显著提高。OPT-FTC纳米颗粒在肝脏中的FTC浓度值增加了2.325倍。在6个月的研究期内，OPT-FTC纳米颗粒被发现相当稳定。因此，所开发的OPT-FTC纳米颗粒可作为药物载体用于持续/延长药物释放和/或降低毒性作用。
