SYNTHESIS OF POLY(ETHYLENE GLYCOL)-POLY(GLUTAMIC ACID)- POLY(ALANINE ACID) TRIBIOCK COPOLYMER AND THE pH-SENSITIVE DRUG DELIVERY OF NANOPARTICLES THEREFROM

Zheng Wang; Shu-fang Yu; Xin Gu; Guo-lin Wu; Yi-nong Wang; Hui Gao; Jian-biao Ma

doi:10.3724/SP.J.1105.2012.11303

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SYNTHESIS OF POLY(ETHYLENE GLYCOL)-POLY(GLUTAMIC ACID)- POLY(ALANINE ACID) TRIBIOCK COPOLYMER AND THE pH-SENSITIVE DRUG DELIVERY OF NANOPARTICLES THEREFROM

Research Article | 更新时间：2021-03-19

- SYNTHESIS OF POLY(ETHYLENE GLYCOL)-POLY(GLUTAMIC ACID)- POLY(ALANINE ACID) TRIBIOCK COPOLYMER AND THE pH-SENSITIVE DRUG DELIVERY OF NANOPARTICLES THEREFROM
- Acta Polymerica Sinica Issue 6, Pages: 599-605(2012)
- 作者机构：
  
  1. 功能高分子材料教育部重点实验室南开大学高分子化学研究所,天津,300071
  2. 天津理工大学化学化工学院天津 300191>
- 作者简介：
- 基金信息：
- DOI：10.3724/SP.J.1105.2012.11303
  CLC：
- Published：20 June 2012，
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Zheng Wang, Shu-fang Yu, Xin Gu, Guo-lin Wu, Yi-nong Wang, Hui Gao, Jian-biao Ma. SYNTHESIS OF POLY(ETHYLENE GLYCOL)-POLY(GLUTAMIC ACID)- POLY(ALANINE ACID) TRIBIOCK COPOLYMER AND THE pH-SENSITIVE DRUG DELIVERY OF NANOPARTICLES THEREFROM. [J]. Acta Polymerica Sinica (6):599-605(2012)
DOI：

Zheng Wang, Shu-fang Yu, Xin Gu, Guo-lin Wu, Yi-nong Wang, Hui Gao, Jian-biao Ma. SYNTHESIS OF POLY(ETHYLENE GLYCOL)-POLY(GLUTAMIC ACID)- POLY(ALANINE ACID) TRIBIOCK COPOLYMER AND THE pH-SENSITIVE DRUG DELIVERY OF NANOPARTICLES THEREFROM. [J]. Acta Polymerica Sinica (6):599-605(2012) DOI： 10.3724/SP.J.1105.2012.11303.

摘要

通过大分子引发剂-胺基--甲氧基聚乙二醇引发N-羧基--氨基环内酸酐开环聚合和酸性水解制备了一种具有pH-响应性的三嵌段共聚物聚乙二醇-聚谷氨酸-聚丙氨酸(mPEG-PLGA-PLAA).通过核磁共振、-电势、动态光散射、电子显微镜等手段表征了此类三嵌段共聚物的自组装过程及所形成胶束的pH-响应性.使用圆二色谱和红外光谱

分析了胶束结构随环境pH值转变过程中聚氨基酸链段二级结构的变化.以阿霉素作为模型药物

研究了三嵌段共聚物的载药能力和在不同pH条件下的药物释放能力.在碱性条件下

PLGA链段去质子化

链段从疏水性变为亲水性

胶束中间层由于水合作用变得松散

药物释放速率增加;在酸性条件下

PLGA链段质子化

不带电荷

与阿霉素药物分子间的静电相互作用消失.同时

PLGA链段-螺旋含量增加

形成由链内氢键维持的刚性棒状结构

将链段周围包埋的药物分子挤出

加速了药物的释放.

Abstract

A novel pH-responsive and biodegradable triblock copolymer

poly(ethylene glycol)-poly(L-glutamic acid)-poly(L-Alanine acid) (PEG-PLGA-PLAA)

was prepared by N -carboxyl anhydride ring-opening polymerization and acidic hydrolysis.It was found that this amphiphilic copolymer can self-assemble into micelles in aqueous solution.The PLAA

PLGA and mPEG segments serve as a hydrophobic core

a pH-responsive shell and a hydrophilic corona

respectively.The morphology and properties of the micelles such as pH sensitivity

zeta potential

secondary structure and mean diameter were investigated.Doxorubicin (DOX) was encapsulated into the micelles to explore the release profiles

which exhibited in vitro pH-dependence.In acidic environment

with the formation of -helix secondary structure of poly(L-glutamic acid) segments

the PLGA segments in the triblock copolymers shrank and relocated in the micelles to trigger the release of drugs.As a result

these DOX-loaded polymeric micelles showed rapid release of DOX from the micelles in weakly acidic environments (pH=5.5) but very slow release under physiological condition (pH=7.4).

关键词

聚天冬氨酸药物释放阿霉素胶束pH-响应

Keywords

Poly(aspartic acid)Drug deliveryDOXMicellepH-Responsive

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Department of Polymer Science and Engneering, Zhejiang University

MOE Key Laboratory of Macromolecular Synthesis and Functionalization

College of Chemistry, State Key Laboratory of Supramolecular Structure and Materials, Jilin University

陕西科技大学教育部轻化工助剂化学与技术重点实验室

The College of Life Sciences, Northwest University

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