PLGA-克班宁纳米粒的制备、表征及体外释药规律分析

目的:制备并表征聚乳酸-羟基乙酸共聚物(PLGA)-克班宁纳米粒(PLGA-Cre-NPs),考察其体外释放特性,为克班宁的体内作用时间延长、毒性降低提供参考。方法:以PLGA为载体,采用乳化溶剂扩散法制备PLGA-Cre-NPs。以包封率、粒径、多分散指数(PDI)为评价指标,通过星点设计-效应面法优选PLGA-Cre-NPs的制备工艺。利用膜透析法考察PLGA-CreNPs的体外释药规律。结果:PLGA-Cre-NPs的最佳制备工艺为有机相与水相体积比(3∶10),丙酮-无水乙醇(8∶2),PLGA投入量90 mg。PLGA-Cre-NPs的包封率(84.69±2.54)%,粒径(155.3±14.2)nm,PDI=0.095±0.018,扫描电镜显示其呈规则球形结构。PLGA-Cre-NPs体外释放包括速释和缓释2个阶段,0~24 h符合Weibull方程,24~168 h符合Higuchi方程;半衰期18.06 h,168 h时累计释放率达78.77%。结论:优选的工艺条件稳定可行。制得的PLGA-Cre-NPs包封率较高、粒径均匀,有望制备成缓释制剂。

Preparation and Characterization of PLGA-crebanine Nanoparticles and Analysis of Its in Vitro Release

Objective: To prepare and characterize poly(lactic-co-glycolic acid) (PLGA)-crebanine nanoparticles (PLGA-Cre-NPs),and evaluate its in vitro release. Method: PLGA-Cre-NPs was prepared by emulsion-solvent diffusion method with PLGA as carrier material.Central composite design-response surface methodology was applied to optimize the preparation procedure of the nanoparticles based on the evaluation indexes of encapsulation rate,particle size and polydispersity index (PDI).The in vitro release kinetics of the nanoparticles was investigated by dynamic dialysis system. Result: The optimized preparation procedure was as follows:volume of organic phase-aqueous phase of 3:10,acetone-ethanol (8:2),PLGA amount of 90 mg.The encapsulation rate of PLGA-Cre-NPs was (84.69±2.54)% with the particle size of (155.3±14.2) nm and PDI of 0.095±0.018,and it showed a regular spherical structure by scanning electron microscopy.Meanwhile,the release profile of PLGA-Cre-NPs could be well described by two phase dynamic equation,0-24 h was closer to Weibull equation,24-168 h was closer to Higuchi equation,and its half life (t_1/2) was 18.06 h,the cumulative release rate was 78.77% at 168 h. Conclusion: PLGA-Cre-NPs has high encapsulation rate and uniform size,which will be expected to become a sustained-release preparation.