多柔比星PLGA纳米粒的处方工艺优化及体外释药行为研究  

Formulation and process optimization of doxorubicin-loaded PLGA nanoparticles and its in vitro release

作　　者：李洁丽[1] 郑春丽[1] 刘建平[1] 朱家壁[1] 

机构地区：[1]中国药科大学药剂研究所,江苏南京210009

出　　处：《药学学报》2013年第5期759-766,共8页Acta Pharmaceutica Sinica

摘　　要：本文以生物可降解材料乳酸羟基乙酸共聚物[poly(lactic-co-glycolic acid),PLGA]为载体,采用复乳化溶剂挥发法制备包载多柔比星(doxorubicin,DOX)的纳米粒(DOX-PLGA NPs)。通过单因素实验考察有机相种类及配比、乳化剂用量、PLGA浓度、外水相与油相体积比(W/O)、药载比、初乳及复乳超声时间、搅拌挥发时间对纳米粒制备的影响;在此基础上以粒径和包封率为评价指标,采用正交实验设计优化纳米粒的处方及最佳制备工艺,以综合加权评分法对测定结果进行分析。对DOX-PLGA NPs的粒径、zeta电位、表观形态、包封率和载药量及体外释药行为进行考察研究。结果得到粒径(189.2±5.3)nm、包封率(73.16±0.43)%和载药量(1.51±0.07)%的优化纳米粒,其体外释放分为突释、缓释两阶段,释放规律符合双相动力学方程,释放终点药物累积释放率为90.34%。结果表明:该PLGA-NPs可实现对亲水性小分子药物的包载。通过处方工艺优化,制得的DOX-PLGA NPs均匀圆整、理化性质稳定,具有良好的药物缓释性能及pH敏感特性,为新型抗肿瘤缓释制剂的开发研究提供了实验基础。Doxorubicin-loaded PLGA nanoparticles （DOX-PLGA NPs） was prepared by double emulsion （W/O/W） solvent evaporation method with the biodegradable materials-poly （lactic-co-glycolic acid） （PLGA） used as carrier materials. Single-factor test was used to investigate the influence of the type and ratio of the organic phase, the amount of surfactant, PLGA concentration, the ratio of external water phase and oil phase （W/O）, the ratio of doxorubicin and PLGA, ultrasonic time and stirring time on the preparation of nanoparticles. The best formulation and preparation conditions were optimized by orthogonal test based on single-factor test, evaluation indicator as particle size and entrapment efficiency, and the results were analyzed by overall desirability. And the in vitro release behaviors of the nanoparticles were studied as well. The size distribution, zeta potential, morphology of DOX-PLGA NPs were characterized by laser light scattering and transmission electron microscopy; encapsulation efficiency and releasing behavior of DOX-PLGA NPs in vitro were investigated by ultraviolet spectrophotometry. The results show that the DOX-PLGA NPs are regularly spherical in shape with the mean size of （189.2±5.3） nm, and the （-potential of the NPs is about （-28.32±0.52） mV. Drug loading and encapsulation efficiency are estimated to be （73.16±0.43） % and （1.51±0.07） %, respectively. The cumulative percentage of the drug released is 90.34%, and the in vitro release behavior made up of initial burst release and sustained-release could be described by the bidirectional kinetic equation. The results indicate that hydrophilic small-molecule drugs could be successfully entrapped into PLGA-NPs. With optimization of the formulation and preparation conditions, we obtained uniform and stable DOX-PLGA NPs with sustained release character in vitro and pH-sensitive property, which could provide the experimental basis for the development of a new anti-tumor sustained-release formulation.

关 键 词：多柔比星 乳酸-羟基乙酸共聚物 纳米粒 复乳化-溶剂挥发法 缓释 PH敏感 

分 类 号：R943[医药卫生—药剂学]