偶联法制备生物降解的聚乳酸-羟基乙酸/聚乙二醇共聚物及其在色素上皮衍生因子载体中的应用
收稿日期: 2016-08-22
修回日期: 2016-09-05
网络出版日期: 2016-09-12
基金资助
国家自然科学基金（No. 81470639）和上海市自然科学基金（No. 14411968400）资助项目.
Preparation of Biodegradable Poly(lactic-co-glycolic acid)/Polyethyle-ne Glycol Copolymer and Its Application as a Carrier for Pigment Epithelium-Derived Factor
Received date: 2016-08-22
Revised date: 2016-09-05
Online published: 2016-09-12
Supported by
Project supported by the National Natural Science Foundation of China(No. 81470639), and the Shanghai Natural Science Foundation(No.14411968400).
以商业化的端羧基聚乳酸-羟基乙酸共聚物（PLGA-COOH）和氨基聚乙二醇羧基（NH2-PEG-COOH）为原料，以生物型分子1-（3-二甲氨基丙基）-3-乙基碳二亚胺盐酸盐（EDC）和N-羟基琥珀酰亚胺（NHS）为媒介，以4-二甲氨基吡啶（DMAP）为催化剂，通过简单、绿色的羧基和胺基的偶联反应，制备了聚乳酸-羟基乙酸/聚乙二醇（PLGA-PEG）共聚物分子，并以该PLGA-PEG分子为载体包裹色素上皮衍生因子（PEDF），得到了PLGA-PEG/PEDF乳剂，并进一步考察了该乳剂作为抑制血管内皮生长因子（VEGF）的潜能.采用核磁共振氢谱表征了PLGA-PEG分子结构及其接枝率，并进一步表征了在不同条件下，PLGA-PEG/PEDF乳剂对人脐静脉内皮细胞（HUVEC）中VEGF水平的抑制作用.结果表明，以偶联法制备的PLGA-PEG分子为载体，得到的PLGA-PEG/PEDF乳剂具有良好的生物安全性，其对VEGF具有较高的抑制作用.
关键词： PLGA-PEG分子; 偶联反应; 色素上皮衍生因子; 血管内皮生长因子
赵俊颖 , 朱艳吉 , 王岩岩 , 朱君 , 沈玺 . 偶联法制备生物降解的聚乳酸-羟基乙酸/聚乙二醇共聚物及其在色素上皮衍生因子载体中的应用[J]. 有机化学, 2017 , 37(1) : 203 -208 . DOI: 10.6023/cjoc201608016
A biodegradable poly(lactic-co-glycolic acid)/polyethylene glycol(PLGA-PEG) copolymer molecule was prepared by the simple and green coupling reaction between carboxyl group of poly(lactide-co-glycolide)-carboxylic acid endcap(PLGA-COOH) and amino group of poly(ethylene glycol) amine and carboxylic acid endcap(NH2-PEG-COOH) in the presence of 1-ethyl-3-[3-dimethylaminopropyl]carbodiimide hydrochloride(EDC) and N-hydroxysuccinimide(NHS).The molecular structure of PLGA-PEG copolymer was characterized by 1H NMR spectroscopy,and the grafting yield of polyethylene glycol(PEG) on poly(lactic-co-glycolic acid)(PLGA) was calculated.Furthermore,pigment epithelium-derived factor(PEDF) was encapsulated in the PLGA-PEG copolymer to prepare a PLGA-PEG/PEDF emulsion for highly efficient inhibition on vascular endothelial growth gene expression(VEGF).The results showed that the obtained PLGA-PEG copolymer was bio-safety and the PLGA-PEG/PEDF emulsion was a good agent for effective inhibition VEGF expression under different conditions.Thus,the PLGA-PEG copolymer can be used as a bio-carrier and the PLGA-PEG/PEDF emulsion can be used as a good angiogenesis inhibitor,which has a potential application for some diseases by anti angiogenesis.
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