尼莫地平PEG-PLGA纳米粒的制备及其处方优化

Preparation and formulation optimization of nimodipine PEG-PLGA nanoparticles

目的:负载尼莫地平的聚乙二醇修饰的聚乳酸-羟基乙酸共聚物[poly(ethylene glycol-poly(lactin-co-glycolic acid),PEG-PLGA)]纳米粒,并对其进行制备工艺、质量评价以及体外释放等相关性研究。方法:以PEG-PLGA为药物载体,采用乳化溶剂挥发法成功制备尼莫地平载药纳米粒。单因素实验和响应面法设计优化处方工艺,透射电子显微镜观察纳米粒形态,激光粒度仪测定其粒径和Zeta电位,HPLC法测定其包封率及载药量并考察其体外释药特性。结果:制备的尼莫地平纳米粒外观呈实心球体,大小均匀且分散性良好;平均粒径为(183.2±3.30) nm, PDI为(0.115±0.049),Zata电位为(-11.78±2.16) mV;平均包封率为84.99%,平均载药量为2.45%;尼莫地平原料药在4 h时基本释放完全(达到95%左右),而尼莫地平纳米粒在4 h时释放仅为43.9%,在第24 h时累计释放度达到(83.66±2.57)%。与对照组相比,制剂组释放缓慢,符合实验设计缓释的要求。结论:本实验成功制备了尼莫地平PEG-PLGA纳米粒,其体外释药具有明显缓释特征,为心脑血管疾病的治疗奠定了基础。

OBJECTIVE To explore preparation processes, quality evaluations and in vitro release of [poly(ethylene glycol-poly(lactin-co-glycolic acid), PEG-PLGA)] nanoparticles loaded with nimodipine and modified by polyethylene glycol.METHODS Using PEG-PLGA as a drug carrier, nimodipine drug-loaded nanoparticles were successfully prepared by emulsification solvent volatilization. Single factor experiment and response surface method were utilized for designing and optimizing the prescription process. The morphology of nanoparticles was observed under transmission electron microscope. Particle size and Zeta potential were measured by a laser particle size analyzer. Encapsulation efficiency and drug loading were measured by high performance liquid chromatography(HPLC) and the in vitro drug release characteristics examined.RESULTS The prepared nimodipine nanoparticles were solid spheres with uniform size and excellent dispersion;average particle size was(183.2±3.30) nm, PDI(0.115±0.049) and Zeta potential(-11.78±2.16) mV;average encapsulation rate 84.99% and average drug loading 2.45%;nimodipine bulk drug released around 95% at 4 h while the release of nimodipine nanoparticles was only 43.9% at 24 h. The cumulative release rate reached 80%. As compared with control group, preparation group released slowly and could fulfill the requirements of experimental design for long circulation.CONCLUSION Nimodipine PEG-PLGA nanoparticles have been successfully prepared. With obvious slow-release characteristics, their in vitro drug release offers rationales for precise treatments of cardiovascular and cerebrovascular diseases.