转铁蛋白修饰的负载三七皂苷R1的PEG-PLGA纳米粒制备及其体外释药评价

Transferrin modified notoginsenoside R1-loaded PEG-PLGA nanoparticles: Preparation and in vitro release evaluation

目的:采用单因素试验与正交试验优化转铁蛋白(Tf)修饰的负载三七皂苷R1的PEG-PLGA纳米粒(R1@Tf-PEG-PLGA NPs)的制备工艺,并对其质量进行评价。方法:采用纳米沉淀法制备负载三七皂苷R1的PEG-PLGA纳米粒(R1@PEG-PLGA NPs),通过单因素试验与正交试验优选其最佳制备条件。将Tf共价偶联在纳米粒表面,制得R1@Tf-PEG-PLGA NPs。以Tf接枝率为指标,通过单因素试验优选其制备条件。采用激光粒度仪和透射电子显微镜对纳米粒进行形态表征及理化参数测定。采用透析法进行纳米粒体外释药研究,并对释药过程进行动力学模型拟合。结果:制得的R1@Tf-PEG-PLGA NPs形态圆整、分散性良好,粒径(153.50±2.01)nm,多分散指数0.11±0.01,Zeta电位(-17.57±1.45)mV,包封率(50.32±0.86)%,载药量(24.26±0.18)%,蛋白接枝率(42.09±0.62)%。药物24 h累积释放率>80%,体外释放过程符合Riger-Peppas动力学模型。结论:制得的R1@Tf-PEG-PLGA NPs粒径均一,包封率与载药量适宜,能够延缓药物的释放。

Objective:To optimize the preparation of transferrin(Tf)modified notoginsenoside R1-loaded PEG-PLGA nanoparticles(R1@Tf-PEG-PLGA NPs)based on single factor experiments and orthogonal design,and evaluate its quality.Methods:Notoginsenoside R1-loaded PEG-PLGA nanoparticles(R1@PEG-PLGA NPs)were prepared by nanoprecipitation method,and the optimum preparation conditions were obtained by single factor experiments and orthogonal design.Then Tf was covalently attached to exterior surface of R1@PEG-PLGA NPs,and R1@Tf-PEG-PLGA NPs were prepared.Taking the grafting rate of Tf as the index,the preparation conditions were optimized by single factor experiments.The morphology and physicochemical properties of nanoparticles were characterized by laser particle size analyzer and transmission electron microscope.The in vitro release of R1@Tf-PEG-PLGA NPs was studied by dialysis method,and the kinetic model of drug release process was analyzed.Results:The prepared R1@Tf-PEG-PLGA NPs were round and well dispersed.The average particle size was(153.50±2.01)nm,the polydispersity index was 0.11±0.01,and the Zeta potential was at(-17.57±1.45)mV.The encapsulation efficiency,drug loading and Tf grafting rate were(50.32±0.86)%,(24.26±0.18)%and(42.09±0.62)%,respectively.The accumulative drug release rate of R1@Tf-PEG-PLGA NPs within 24 hours was more than 80%.The in vitro release process of the prepared nanoparticles was accorded with Riger-Peppas model.Conclusion:The prepared R1@Tf-PEG-PLGA NPs show the uniform particle size,with suitable encapsulation efficiency and drug loading,which could delay the drug release.