Preparation and in vitro Studies of Stealth PEGylated PLGA Nanoparticles as Carriers for Arsenic Trioxide  

作　　者：王志清 刘卫 徐辉碧 杨祥良 

机构地区：[1]College Of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China [2]Department of Chemistry, Huazhong University of Science and Technology, Wuhan 430074, China

出　　处：《Chinese Journal of Chemical Engineering》2007年第6期795-801,共7页中国化学工程学报（英文版）

基　　金：Supported by the Special Funds for Major State Basic Research Program of China (973 Program, No.2007CB935800);theNational High Technology Research and Development Program of China (863 Program, No.2004AA215162).

摘　　要：The aim of this study was to prepare arsenic trioxide （ATO）-loaded stealth PEGylated PLGA nanoparticles （PEG-PLGA-NPs） and to assess the merits of PEG-PLGA-NPs as drug carriers for ATO delivery. PEG-PLGA copolymer was synthesized with methoxypolyethyleneglycol （Mw=5000）, D, L-lactide, and glycolide by the ring-opening polymerization method. Amorphous ATO was transformed into cubic crystal form to increase its solu-bility in the organic solvent. ATO-loaded PEG-PLGA-NPs were prepared by the modified spontaneous emulsification solvent diffusion （SESD） method, and the main experimental factors influencing the characteristics of nanopar- ticles were investigated, to optimize the preparation. To confirm the escape of PEG-PLGA-NPs from phagocytosis by phagocytes, PEG-PLGA-NPs labeled rhodamine B uptake by murine peritoneal macrophages （MPM） were analyzed by flow cytometry. The results showed that the physicochemical characteristics of PEG-PLGA-NPs were affected by the type and concentration of the emulsifiers, polymer concentration, and drug concentration. ATO-loaded PEG-PLGA-NPs, with particle size of 120.8nm, zeta potential of-10.73mV, encapsulation efficiency of 73.6%, and drug loading of 1.36%, were prepared under optimal conditions. The images of transmission electron micros-copy （TEM） indicated that the optimized nanoparticles were near spherical and without aggregation or adhesion. The release experiments in vitro showed the ATO release from PEG-PLGA-NPs exhibited consequently sustained release for more than 26d, which was in accordance with Higuchi equation. The uptake of PEG-PLGA-NPs by MPM was found to decrease markedly compared to PLGA-NPs. The experimental results showed that PEG-PLGA-NPs were potential nano drug delivery carriers for ATO.学习是准备砷三氧化物(ATO ) 的这的目的装载了秘密 PEGylated PLGA nanoparticles (PEG-PLGA-NPs ) 并且为 ATO 作为药搬运人估计 PEG-PLGA-NPs 的优点交货。PEG-PLGA 共聚物与 methoxypolyethyleneglycol 被综合(Mw = 5000 ) ，由戒指洞聚合方法的 D， L 减水乳酸，和 glycolide。非结晶的 ATO 被转变成立方的水晶形式在器官的溶剂增加它的溶解度。装载 ATO 的 PEG-PLGA-NPs 被修改自发的乳化溶剂散开(SESD ) 准备方法，和影响 nanoparticles 的特征的主要试验性的因素被调查，到优化准备。由吞噬细胞从吞噬作用证实 PEG-PLGA-NPs 的逃跑，鼠科的腹巨噬细胞(MPM ) 标记玫瑰精 B 举起的 PEG-PLGA-NPs 被流动 cytometry 分析。结果证明 PEG-PLGA-NPs 的物理化学的特征被 emulsifiers，聚合物集中，和药集中的类型和集中影响。装载 ATO 的 PEG-PLGA-NPs 与 120.8nm 的粒子尺寸，希腊语的第六个字母潜力 - 10.73mV， 73.6% 的封装效率，和 1.36% 装载的药，在最佳的条件下面被准备。传播电子显微镜学(TEM ) 的图象显示优化 nanoparticles 是近球形的并且没有聚集或粘附。在 vitro 的版本实验证明从因而展出的 PEG-PLGA-NPs 的 ATO 版本为超过 26d 支撑了版本，它根据 Higuchi 方程。由 MPM 的 PEG-PLGA-NPs 的举起被发现与 PLGA-NPs 相比显著地减少。试验性的结果证明 PEG-PLGA-NPs 是为 ATO 的潜在的 nano 药交货搬运人。

关 键 词：arsenic trioxide PEGylated-PLGA nanoparticles ring-opening polymerization spontaneous emulsification solvent diffusion method in vitro drug release phagocytic uptake 

分 类 号：TQ460[化学工程—制药化工]