正交优化聚乳酸-羟基乙酸纳米粒的制备

Preparation of orthogonal optimized paclitaxel-loaded polylactide-co-glycolide nanoparticles

背景:聚乳酸-羟基乙酸纳米粒或纳米微球用于制备生物降解型缓释或定向给药体系已经研究了近30年,是国内外研究的热点。该体系能够控制粒径大小、延缓药物降解、延长药物释放时间、靶向释放、降低药物毒性和刺激性等。目的:以紫杉醇为模型药物、聚乳酸-羟基乙酸为包裹材料,探索载药纳米粒的制备条件对粒径、包封率等的影响,确定最佳制备工艺条件。方法:采用乳化-溶剂挥发法制备聚乳酸-羟基乙酸纳米粒,以粒径、包封率和载药量等为观察指标,通过正交设计法优化纳米粒制备工艺条件。结果与结论:通过正交实验设计,优化了制备工艺条件,其最佳条件是超声乳化时间为15min,乳化剂浓度为1%,油水相比为1∶25,合成温度为25℃。在此条件下进行实验,制备出的载药纳米粒粒径为217.6nm,载药量1.79%,包封率85%。该制备工艺简单、稳定,优化制备条件,可制备出包封率高、粒径适宜的紫杉醇-聚乳酸-羟基乙酸纳米粒。

BACKGROUND： Polylactide-co-glycolide （PLGA） nanoparticles or nano-preparation of biodegradable microspheres for sustained release or targeted delivery system have been studied for almost 30 years, considered as a hot spot of research. The system can control the particle size, delay drug degradation, prolong drug release time, conduct targeted release, reduce drug toxicity and irritation. OBJECTIVE： To explore the preparation method of the drug-loaded nanoparticles on particle size, encapsulation efficiency and other effects, and to determine the optimal preparation conditions using paclitaxel as a model drug and PLGA as the coating material. METHODS： PLGA nanoparticles were prepared using emulsion-solvent evaporation technique. The particle size of nanoparticles was measured, and the encapsulation efficiency and drug loading of the nanoparticles were calculated. The preparation techniques of nanoparticles were optimized by orthogonal method. RESULTS AND CONCLUSION： Through orthogonal test, the preparation techniques of nanoparticles were optimized. The optimization parameters are 15 minutes ultrasonic emulsification, 1% concentration of emulsifier, organic to water ratio of 1： 25, temperature 25 ℃. Under these conditions, the prepared nanoparticles size was 217.6 nm, drug loading was 1.79%, encapsulation efficiency was 85%. The preparation process is simple, stable and optimized. The paclitaxel-PLGA appropriate nanoparticles can be prepared at a high entrapment efficiency and suitable particle size.