PEGylated PLGA nanoparticles as protein carriers: synthesis, preparation and biodistribution in rats
PEGylated PLGA nanoparticles as protein carriers: synthesis, preparation and biodistribution in rats
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DOI：
10.1016/s0168-3659(01)00218-8
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发表时间：
2001-04-02
影响因子：
10.8
通讯作者：
Gao, XJ
中科院分区：
文献类型：
--
作者：
Li, YP;Pei, YY;Gao, XJ
本工作的目的是评估聚乙二醇化聚乳酸-羟基乙酸共聚物（PEG-PLGA）纳米粒作为蛋白质和肽类药物（PPD）载体的优点。以聚乙二醇（MePEG）和聚乳酸-羟基乙酸共聚物（PLGA）为原料，合成了PEG-PLGA共聚物，可用于制备隐形纳米粒或长循环纳米粒。用核磁共振氢谱和傅里叶变换红外光谱对PEG-PLGA的结构进行了表征，用凝胶渗透色谱法测定了PEG-PLGA的分子量。以牛血清白蛋白（BSA）为模型蛋白，采用复乳法将其包裹在隐形纳米粒中。颗粒的大小，zeta电位和蛋白质的体外释放方面进行了表征。在大鼠中，在静脉内施用后，在24小时内测定负载BSA的纳米颗粒的生物命运。实验结果表明，在MePEG存在下，丙交酯和乙交酯开环聚合可得到PEG-PLGA。1H-1 NMR和FTIR光谱与PEG-PLGA共聚物的结构一致。通过GPC测定的分子量为50800。采用复乳法制备了BSA隐形纳米粒子。包封率为48.6%，粒径约200 nm，Zeta电位为-16.1 mV。BSA从隐形纳米粒中的释放呈现出先突释后缓释的过程。与PLGA纳米粒相比，PEG-PLGA纳米粒可使BSA的半衰期从13.6min延长至4.5h，并明显改变BSA在大鼠体内的生物分布。就这样。PEG-PLGA纳米粒可作为PPD的有效载体。(C)2001 Elsevier Science B. V.保留所有权利。
The aim of the present work was to assess the merits of PEGylated poly( lactic-co-glycolic acid) (PEG-PLGA) nanoparticles as protein and peptide drugs (PPD) carriers. PEG-PLGA copolymer, which could be used to prepare the stealth nanoparticles or long-circulating nanoparticles, was synthesized with methoxypolyethyleneglycol (MePEG) and PLGA. The structure of PEG-PLGA was confirmed with H-1 NMR and Fourier transform infrared (FTIR) spectrum, and molecular weight was determined by gel permeation chromatography (GPC). Bovine serum albumin (BSA), chosen as model protein, was encapsulated within the stealth nanoparticles with the double emulsion method. The particles were characterized in terms of size, zeta potential and in vitro release of the protein. The biological fate of the BSA-loaded nanoparticles following intravenous administration was determined over 24 h in rats. The experimental results showed that PEG-PLGA could be obtained by ring-opening polymerization of lactide and glycolide in the presence of MePEG. H-1 NMR and FTIR spectrum were consistent with the structure of PEG-PLGA copolymer. Molecular weight determined by GPC was 50800. The stealth nanoparticles loading BSA could be prepared by the double emulsion technique. The entrapment efficiency was 48.6%, particle size about 200 nm and zeta potential -16.1 mV. BSA release from the stealth nanoparticles showed an initial burst release and then sustained release. PEG-PLGA nanoparticles could extend half-life of BSA from 13.6 min of loaded in PLGA nanoparticles to 4.5 h and obviously change the protein biodistribution in rats compared with that of PLGA nanoparticles. Thus. PEG-PLGA nanoparticles could be an effective carrier for PPD delivery. (C) 2001 Elsevier Science B.V. All rights reserved.