载三氧化二砷的PEG-PLGA隐性纳米粒的制备及体外研究

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载三氧化二砷的PEG-PLGA隐性纳米粒的制备及体外研究

王志清¹; 刘卫¹; 徐辉碧²; 杨祥良¹

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

收稿日期:2007-01-03 修回日期:1900-01-01 出版日期:2007-12-28 发布日期:2007-12-28
通讯作者: 王志清

Preparation and in vitro studies of stealth PEGylated PLGA nanoparticles as carriers for arsenic trioxide

WANG Zhiqing¹; LIU Wei¹; XU Huibi²; YANG Xiangliang¹

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

Received:2007-01-03 Revised:1900-01-01 Online:2007-12-28 Published:2007-12-28
Contact: WANG Zhiqing

摘要/Abstract

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 emulsifica-tion 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 ana-lyzed by flow cytometry. The results showed that the physicochemical characteristics of PEG-PLGA-NPs were af-fected 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.

关键词: arsenic trioxide;PEGylated PLGA nanoparticles;ring-opening polymerization;spontaneous emulsification solvent diffusion method;in vitro drug release;phagocytic uptake

Abstract: 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 emulsifica-tion 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 ana-lyzed by flow cytometry. The results showed that the physicochemical characteristics of PEG-PLGA-NPs were af-fected 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.

Key words: arsenic trioxide, PEGylated PLGA nanoparticles, ring-opening polymerization, spontaneous emulsification solvent diffusion method, in vitro drug release, phagocytic uptake

王志清, 刘卫, 徐辉碧, 杨祥良. 载三氧化二砷的PEG-PLGA隐性纳米粒的制备及体外研究[J]. CIESC Journal.

WANG Zhiqing, LIU Wei, XU Huibi, YANG Xiangliang. Preparation and in vitro studies of stealth PEGylated PLGA nanoparticles as carriers for arsenic trioxide[J]. .

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载三氧化二砷的PEG-PLGA隐性纳米粒的制备及体外研究

Preparation and in vitro studies of stealth PEGylated PLGA nanoparticles as carriers for arsenic trioxide

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