星点设计-响应曲面法优化IMP-RH60/mPEG-PLLA胶束的处方工艺及其体外评价  

Optimization of the formulation of IMP-RH60/mPEG-PLLA micelles by central composite design-response surface methodology and its evaluation in vitro

作　　者：李秋香 董伟 周爱鲜 赵国巍 鲁永锋 时尚 梁新丽 LI Qiu-xiang;DONG Wei;ZHOU Ai-xian;ZHAO Guo-wei;LU Yong-feng;SHI Shang;LIANG Xin-li(Key Laboratory of Modern Preparation of Traditional Chinese Medicine,Ministry of Education,Jiangxi University of Traditional Chinese Medicine,Nanchang 330004,China)

机构地区：[1]江西中医药大学现代中药制剂教育部重点实验室,南昌330004

出　　处：《中国新药杂志》2024年第10期1032-1042,共11页Chinese Journal of New Drugs

基　　金：国家自然科学基金资助项目(82060733);江西中医药大学中药制剂技术与装备创新团队资助项目(CXTD22006)。

摘　　要：目的:通过星点设计-响应曲面法优化欧前胡素-聚氧乙烯氢化蓖麻油/甲氧基聚乙二醇聚乳酸[imperatorin micelles loaded with Cremophor?RH 60/monomethoxy poly(ethylene glycol)-block-poly(L-lactide),IMP-RH60/mPEG-PLLA]胶束的处方工艺。方法:在单因素考察的基础上,以RH60用量、药物与载体比例、水相体积为自变量,包封率和载药量为因变量,进行三因素三水平的星点设计-响应面法实验,分析结果得到IMP-RH60/mPEG-PLLA胶束的最优处方,并对胶束的释放和摄取进行评估。结果:确定最优处方工艺条件为:RH60的投药量为28 mg,IMP投药量为1.2 mg,mPEG-PLLA投药量为10 mg,水化体积为6 mL,在此条件下得到的胶束粒径为(25.48±0.92)nm,Zeta电位为-(5.50±1.06)mV,平均包封率为(85.78±0.84)%,平均载药量为(2.66±0.03)%。体外评价结果表明胶束释放效果优于原料药,并增强了药物的摄取。结论:星点设计-响应曲面法所建立的模型精密度高,可用于IMP-RH60/mPEG-PLLA胶束的处方工艺优化。Objective:To optimize the preparation process of imperatorin micelles loaded with Cremophor RH 60/monomethoxy poly(ethylene glycol)-block-poly(L-lactide)(IMP-RH60/mPEG-PLLA)by central composite design-response surface methodology.Methods:On the basis of single factor investigation,the dosage of RH60,the ratio of drug and carrier and the water volume were taken as independent variables,the entrapment rate and loading capacity were determined as dependent variables.Central composite design-response surface methodology was used to carry out three factors and three levels experiment,and the results were analyzed to get the optimal prescription process.The micelles release was evaluated by in vitro release behavior and cellular uptake.Results:The optimal prescription of IMP-RH60/mPEG-PLLA micelles was determined as follows:the dosage of RH60 was 28 mg,the dosage of IMP was 1.2 mg,the dosage of mPEG-PLLA was 10 mg,and the water volume was 6 mL.The IMP-RH60/mPEG-PLLA micelles prepared under these conditions had an average particle size of(25.48±0.92)nm,Zeta potential of-(5.50±1.06)mV,entrapment rate of(85.78±0.84)%,and the loading capacity of IMP was(2.66±0.03)%.The in vitro release test showed that the release of IMP from IMP-RH60/mPEGPLLA micelles was significantly better than that of IMP API,and the results of cellular uptake test indicated that IMP-RH60/mPEG-PLLA micelles could promote the uptake of IMP.Conclusion:The mathematic model established by central composite design-response surface methodology has high accuracy and could be used to optimize the formulation of IMP-RH60/mPEG-PLLA micelles preparations.

关 键 词：欧前胡素 胶束 星点设计-响应曲面法 体外释放 细胞摄取 

分 类 号：R943.42[医药卫生—药剂学] R979.1[医药卫生—药学]