包载马钱子碱聚乳酸-羟基乙酸共聚物纳米粒处方工艺优化及其特性研究  

Optimization of formulation and characteristics of PLGA nanoparticles containing brucine

作　　者：管庆霞[1] 夏昭睿 王艳宏[1] 张雪[1] 李伟男[1] 杨志欣[1] 王锐[1] 李秀岩[1] 冯宇飞[1] GUAN Qing-xia;XIA Zhao-rui;WANG Yan-hong;ZHANG Xue;LI Wei-nan;YANG Zhi-xin;WANG Rui;LI Xiu-yan;FENG Yu-fei(College of Pharmacy,Heilongjiang University of Chinese Medicine,Harbin 150040,China)

机构地区：[1]黑龙江中医药大学,黑龙江哈尔滨150040

出　　处：《中草药》2021年第4期951-961,共11页Chinese Traditional and Herbal Drugs

基　　金：国家自然科学基金青年基金项目(81703944);黑龙江省自然科学基金优秀青年项目(YQ2019H031);黑龙江中医药大学“优秀创新人才支持计划”项目(2018年)。

摘　　要：目的对包载马钱子碱(brucine)聚乳酸-羟基乙酸共聚物[poly(lactic-co-glycolic acid),PLGA](B-PLGA)纳米粒进行处方与工艺优化。方法采用沉淀法制备B-PLGA纳米粒,以平均粒径、多分散系数(PDI)、Zeta电位、包封率和载药量为评价指标,采用单因素考察法结合星点设计-效应面法(CCD-RSM)筛选B-PLGA纳米粒的最优处方,并将最优处方进行表征及体外释放实验。结果最优处方选择丙酮作为有机溶剂,泊洛沙姆188(F68)作为稳定剂,超声时间为1 min,磁力搅拌速度为900 r/min,磁力搅拌时间为30 min,F68用量为0.35%,载体用量为25 mg,药物用量为1.0 mg,有机相与水相的比为0.54。所制得的B-PLGA纳米粒为淡蓝色乳光透明液体,粒径为(97.12±4.23)nm,PDI为0.098±0.035,Zeta电位为(-27.30±0.31)m V,包封率为(69.24±1.42)%,载药量为(2.65±0.03)%。通过表征,纳米粒形态完整,通过体外释放实验得知,纳米粒体外释放拟合符合Higuchi方程。结论星点设计-效应面法可用于包载马钱子碱PLGA纳米粒处方与工艺优化,且优化后的纳米粒具有缓释作用。Objective To optimize the formulation and process of poly(lactic-co-glycolic acid)(PLGA) nanoparticles containing brucine(B-PLGA). Methods The precipitation method was used to prepare B-PLGA nanoparticles, and the particle size, polydispersity coefficient(PDI), Zeta potential, encapsulation efficiency, and drug loading were used as evaluation indicators. The single factor investigation method combined with the central composite design-response surface method(CCD-RSM) were used to screen the optimal formulation of B-PLGA nanoparticles, and the characterization and in vitro release experiments on the optimal formulation were performed. Results Acetone and Poloxamer 188(F68) were selected as the organic solvent and the stabilizer for the optimal prescription, the ultrasonic time was 1 min, the magnetic stirring speed was 900 r/min, the magnetic stirring time was 30 min, the F68 concentration was 0.35%, the carrier dosage was 25 mg, the drug dosage was 1.0 mg. The ratio of organic phase to water phase was 0.54. The prepared B-PLGA nanoparticles were light blue opalescent transparent liquid with a particle size of(97.12 ± 4.23) nm, a PDI of 0.098 ± 0.035, a Zeta potential of(-27.30 ± 0.31) mV, and an encapsulation efficiency of(69.24 ± 1.42)%, and the drug loading was(2.65 ± 0.03)%. Through characterization, the morphology of the nanoparticles was complete, and the in vitro release experiment showed that the in vitro release fit of the nanoparticles conforms to the Higuchi equation. Conclusion The method is stable and feasible, which can be used for the formulation and process optimization of PLGA nanoparticles containing brucine, and the optimized nanoparticles have slow-release effect.

关 键 词：马钱子碱 聚乳酸-羟基乙酸共聚物 纳米粒 沉淀法 单因素考察法 星点设计-效应面法 体外释放 HIGUCHI方程 缓释作用 

分 类 号：R283.6[医药卫生—中药学]