星点设计-效应面法优化PLGA-PEG纳米粒的处方工艺  

Optimization of Formula and Preparation Process of PLGA-PEG Nanoparticles by Central Composite Design-Response Surface Methodology

作　　者：林雯[1] 史琼枝 李银科 纪刚剑 谢向阳 胡华 李振华[4] Lin Wen;Shi Qiongzhi;Li Yinke;Ji Gangjian;Xie Xiangyang;Hu Hua;Li Zhenhua(Department of Clinical Laboratory,Huangshi Love&Health Hospital,Hubei Huangshi 435000,China;Department of Pharmacy,General Hospital of Central Theater Command of the PLA;Department of Pharmacy,Wuhan Third Hospital(Tongren Hospital of Wuhan University);Department of Respiratory and Critical Care Medicine,Wuhan Central Hospital)

机构地区：[1]黄石爱康医院检验科,湖北黄石435000 [2]中国人民解放军中部战区总医院药剂科 [3]武汉市第三医院(武汉大学同仁医院)药学部 [4]武汉市中心医院呼吸与危重症医学科

出　　处：《中国药师》2022年第8期1323-1327,共5页China Pharmacist

基　　金：湖北省自然科学基金项目(编号:2020CFB569);湖北省卫生计生科研基金项目(编号:WJ2018H0116&WJ2021M218)。

摘　　要：目的:采用星点设计-效应面法优化载体基质为PLGA-PEG的siRNA纳米粒的制备工艺。方法:采用复乳法制备载药纳米粒,以二氯甲烷体积、吐温-80的质量分数和复乳的超声时间为试验因素,纳米粒的平均粒径、包封率和突释量为考察指标,根据星点设计原理安排实验和处方工艺优化。结果:成功制备了纳米粒。最佳工艺为二氯甲烷体积13 ml,乳化剂吐温-80的质量分数为3.1%,复乳的超声时间为2.8 min;按优化处方工艺制备的纳米粒的平均粒径(101.5±6.3)nm,包封率(57.6±4.8)%,体外48 h累积释放度高于80%。结论:星点设计-效应面法适用于PLGA-PEG纳米粒的工艺优化,所建立的数学模型预测性良好。Objective: To optimize the formula of PLGA-PEG nanoparticles loaded with siRNA by central composite design-response surface methodology. Methods: The nanoparticles were prepared by a double emulsion method. The volume of dichloromethane, mass fraction of Tween-80 and ultrasonic time of compound emulsion were taken as the experimental factors, and the mean particle size, entrapment efficiency and burst release were selected as the evaluation indexes. According to the principles of central composite design, experiments and related preparation process were arranged and conducted. Results: PLGA-PEG nanoparticles were successfully prepared. The optimal formula was as follows: 13 ml dichloromethane, 3.1% Tween-80 and 2.8 min ultrasonic time. The obtained nanoparticles were characterized with the mean particle size of(101.5±6.3) nm, siRNA entrapment efficiency of(57.6±4.8)% and in vitro drug release over 80% in 48 h. Conclusion: Central composite design-response surface methodology is suitable for the optimization of PLGA-PEG nanoparticles, and the established mathematical model has a good predictability for such preparation.

关 键 词：星点设计 聚乳酸-羟基乙酸共聚物-聚乙二醇 纳米粒 小干扰RNA 

分 类 号：R944.9[医药卫生—药剂学]