PLGA-克班宁纳米粒的制备、表征及体外释药规律分析  

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

作　　者：程欣[1] 孔淑君 王辉[1] 黄秋艳[1] 汪红梅[1] 马云淑[1] CHENG Xin;KONG Shu-jun;WANG Hui;HUANG Qiu-yan;WANG Hong-mei;MA Yun-shu(Yunnan Key Laboratory of Dai and Yi Medicines, College of Pharmaceutical Sciences, Yunnan University of Traditional Chinese Medicine, Kunming 650500, China;Disha Pharmaceutical Group Co. Ltd. , Weihai 264205, China)

机构地区：[1]云南中医学院中药学院云南省傣医药与彝医药重点实验室,昆明650500 [2]迪沙药业集团有限公司,山东威海264205

出　　处：《中国实验方剂学杂志》2018年第9期9-14,共6页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家自然科学基金项目(81260651,81673682);云南省科技厅-云南中医学院应用基础研究联合专项(2015FB205-003,2017FF117-017);云南省重点实验室培育计划项目(2017DG006)

摘　　要：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。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（t1/2） 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.

关 键 词：克班宁 聚乳酸-羟基乙酸共聚物 纳米粒 星点设计-效应面法 缓释制剂 体外释药性能 乳化溶剂扩散法 

分 类 号：R22[医药卫生—中医基础理论] R289[医药卫生—中医学]