口服胸腺五肽乳酸-羟基乙酸共聚物纳米粒的制备及物理性质考察

目的制备供口服给药的胸腺五肽乳酸-羟基乙酸共聚物(thymopentin-poly lactic-co-glycolicacid;TP5-PLGA)纳米粒,并对纳米粒的物理性质进行考察。方法用复乳-溶剂挥发法制备TP5-PLGA纳米粒,以包封率为评价指标,用L16(45)正交设计优选纳米粒制备的处方工艺条件,用HPLC法测定胸腺五肽的含量,用激光粒度仪测定纳米粒的粒径,用透射电镜观察纳米粒的形态,用动态透析法考察纳米粒的体外释药特征。结果正交设计确定纳米粒制备的最优处方工艺条件为胸腺五肽质量浓度50 g.L-1,载体材料PLGA质量浓度100 g.L-1,乳化剂PVA质量浓度20 g.L-1;优化处方与工艺制备的纳米粒为规整的圆球形,平均粒径为(150.3±9.6)nm,载药量与包封率分别为(2.403±0.066)%与(28.12±0.60)%;体外释药结果表明,前5 h药物释放(31.27±1.5)%,存在一定突释,4 d累积释药量为(43.60±2.3)%。结论以乳酸-羟基乙酸共聚物为载体材料制备胸腺五肽纳米粒工艺简便,制剂具有良好的物理性质和体外释药特征。

Preparation and physical characterization of poly-lactic-co-glycolic acid nanoparticles loaded with thymopentin for oral administration

Objective To design and evaluate the characteristics of polylactic-co-glycolic acid nanoparticles loaded with thymopentin(TP5-PLGA nanoparticles) for oral administration.Methods The TP5-PLGA nanoparticles were prepared by using a double emulsion-solvent evaporation technique.The preparation techniques were optimized by means of an orthogonal test design with entrapment efficiency as index of investigation.The concentration of thymopentin(TP5) was determined by established HPLC method.The mean diameter and size distribution of performed nanoparticles were determined by laser particle sizer.The morphology of nanoparticles was observed by transmission electron microscopy.Drug release was studied using a dialysis method in vitro.Results TP5-PLGA nanoparticles were prepared in an optimized techniques with TP5 concentration of 50 g·L-1,polylactic-co-glycolic acid(PLGA) concentration of 100 g·L-1 and poly-(vinyl alcohol)(PVA) concentration of 20 g·L-1.The prepared nanoparticles were regular spheres with an average diameter of(150.3±9.6) nm.The drug loading and encapsulation efficiency were(2.403±0.066) % and(28.12±0.60) %,respectively.There was(31.27±1.5) % of encapsulated TP5 released in PBS(pH 7.4,0.05 mol·L-1) at the first 5 h that reflected a burst effect.On the 4th day,(43.60±2.3) % of encapsulated TP5 was released in vitro.Conclusions The method for preparing TP5-PLGA nanoparticles is simple and convenient.The prepared nanoparticles possess good physical performance and sustained release character in vitro.