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基于具有靶向癌症治疗性能的自组装刷状 PLGA/PEG/AEMA 共聚物的 pH 响应和叶酸纳米粒子的合成与表征:全面的动力学研究。

Synthesis and characterization of pH-responsive and folated nanoparticles based on self-assembled brush-like PLGA/PEG/AEMA copolymer with targeted cancer therapy properties: A comprehensive kinetic study.

机构信息

Polymer Chemistry Department, School of Science, University of Tehran, PO Box 14155-6455, Tehran, Iran.

出版信息

Eur J Med Chem. 2012 Apr;50:416-27. doi: 10.1016/j.ejmech.2012.02.027. Epub 2012 Feb 22.

Abstract

In this study, a novel nanocarrier was synthesized based on methacrylated poly(lactic-co-glycolic acid) (mPLGA) as a lipophilic domain, acrylated methoxy poly(ethylene glycol) (aMPEG) as hydrophilic part and N-2-[(tert-butoxycarbonyl)amino] ethyl methacrylamide (Boc-AEMA) as pH-responsive segment. Radical polymerization of the above-mentioned three modified monomers produces amphiphilic brush-like copolymer. The protecting amine group (Boc) was selectively deprotected and the latter targeted copolymer was produced through the reaction of this copolymer with activated folic acid. Nanoprecipitation method was used to prepare quercetin-loaded nanoparticles. Dynamic light scattering (DLS) analysis showed that the produced nanoparticles had nanometric size (<100nm) and low polydispersity in size at different pHs. Higuchi and Korsmeyer-Peppas models were applied to evaluate release mechanisms and kinetics. Based on in-vitro degradation study, we found that the brush-like copolymer underwent a rapid weight loss in acidic pH.

摘要

在这项研究中,合成了一种新型纳米载体,该载体以甲基丙烯酰化聚(乳酸-共-乙醇酸)(mPLGA)为亲脂性部分,丙烯酰化甲氧基聚乙二醇(aMPEG)为亲水性部分,N-2-[(叔丁氧羰基)氨基]乙基甲基丙烯酰胺(Boc-AEMA)为 pH 响应性部分。上述三种改性单体的自由基聚合产生两亲性刷状共聚物。通过选择性脱保护伯胺基团(Boc),并通过该共聚物与活化叶酸的反应,得到了靶向共聚物。采用纳米沉淀法制备了槲皮素负载的纳米颗粒。动态光散射(DLS)分析表明,所制备的纳米颗粒在不同 pH 值下具有纳米级尺寸(<100nm)和低尺寸多分散性。Higuchi 和 Korsmeyer-Peppas 模型被用于评估释放机制和动力学。根据体外降解研究,我们发现刷状共聚物在酸性 pH 下会迅速失重。

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