利福喷丁/聚乳酸-羟基乙酸纳米粒的制备及处方工艺优化

Preparation and optimization of rifapentine-loaded poly(lactic-co-glycolic acid)(PLGA)-based nanoparticles

目的:研制负载利福喷丁的聚乳酸-羟基乙酸共聚物[poly(lactic-co-glycolic acid),PLGA]纳米粒,并对其处方及制备工艺进行优化。方法:采用快速膜乳化法制备利福喷丁/PLGA纳米粒。通过单因素实验考察了乳化剂浓度、PLGA浓度、油相/水相体积比、初乳制备转速、初乳制备时间、过膜压力、过膜次数对纳米粒制备的影响。在此基础上以粒径、载药率、包封率为评价指标,使用正交实验设计对纳米粒制备的处方工艺进行优化,以TOPSIS法进行多指标综合分析。然后对最优处方工艺进行验证,并对载药纳米粒的体外释药行为进行考察。结果:经最优处方工艺制备的载药纳米粒,粒径(428±11.4)nm,粒径分布为(0.186±0.036),包封率为(76.89±2.6)%,载药率为(10.89±1.2)%。用透视电镜观察呈均匀分布的球形。在体外药物释放实验中,药物在72 h内累计释放了78.81%。结论:采用快速膜乳化可以简单快捷地制备均匀圆整、包封性好、具有良好缓释性能的利福喷丁/PLGA纳米粒,并为新型抗结核精准治疗的开发提供了基础。

OBJECTIVE To prepare rifapentine/PLGA nanoparticles and optimize its formulation and preparation.METHODS The rifapentine/PLGA nanoparticles were prepared by premixed membrane emulsification.The single-factor experiment was used to investigate the effects of emulsifier concentration,PLGA concentration,oil phase/water phase volume ratio(O/W),tansmembrane pressure,number of extrusions,premix speed and time.The formulation and process were optimized by orthogonal experiment based the single-factor experiment using the particle size,drug loading rate and encapsulation efficiency as the evaluation indexes.The results were comprehensively analyzed by the TOPSIS method.Then the optimal formulation process was validated,and the in vitro drug release behavior of drug-loaded nanoparticles was investigated.RESULTS The nanoparticles were prepared by the optimal formulation process,the mean size was(428±11.4)nm,the polydispersity index(PDI)was about(0.186±0.036),the encapsulation efficiency was(76.89±2.6)%,and the drug loading rate was(10.89±1.2)%.The spherical distribution of nanoparticles was observed by transmission electron microscope.The cumulative percentage of the drug relesed was 78.81%during 72 hours in vitro release behavior.CONCLUSION Rifapentine/PLGA nanoparticles with uniform roundness,good encapsulation and good sustained-release properties can be simply and quickly prepared by rapid membrane emulsification,which provides a basis for the development of new anti-tuberculosis precise treatment..