High Molecular Weight Biodegradable Poly(ethylene glycol) via Carboxyl-Ester Transesterification
High Molecular Weight Biodegradable Poly(ethylene glycol) via Carboxyl-Ester Transesterification
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通过羧基酯酯交换制备高分子量可生物降解聚乙二醇
DOI：
10.1021/acs.macromol.9b02177
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发表时间：
2020-03-24
期刊：
影响因子：
5.5
通讯作者：
Zhu, Weipu
中科院分区：
文献类型：
--
作者：
Cai, Qiuquan;Li, Xiaodong;Zhu, Weipu
聚乙二醇(PEG)被广泛应用于治疗分子的共价偶联，以延长其生物循环时间。通过增加聚乙二醇的相对分子质量，可以进一步提高这一效果。然而，由于缺乏有效的降解机制，分子量超过10 kDa的聚乙二醇酯很难从体内排泄出来，从而在肝脏和肾脏积聚，增加了毒性风险。本文通过聚乙二醇二元酸的缩聚反应，将聚乙二醇酯键连接在聚乙二醇酯键上，合成了可生物降解的聚乙二醇酯。为了克服传统的酯化方法合成高分子量产物的困难，提出了一种新的羧基酯交换反应机理来制备分子量高达112.6 kDa的可生物降解的聚乙二醇酯。研究证实，这些可生物降解的聚乙二醇酯具有类似分子量的不可降解聚乙二醇酯的特性，但它们可以在酯键裂解后被代谢。
Poly(ethylene glycol) (PEG) is widely used for covalent conjugation with therapeutic molecules to prolong their biocirculation time. This effect can be further improved by increasing the molecular weight of PEG. However, because of the lack of effective degradation mechanisms, PEG with a molecular mass over 10 kDa is hardly excreted from the body, thus accumulating in the liver and kidneys which increases the risk of toxicity. Herein, biodegradable PEGs were synthesized by linking PEG backbones with ester bonds through the polycondensation of PEG diols and dicarboxylic acids. To overcome the difficulties in synthesis of high molecular weight products by traditional esterification strategies, a novel carboxyl-ester transesterification mechanism was developed to produce biodegradable PEGs with a molecular weight up to 112.6 kDa. It was confirmed that these biodegradable PEGs show comparable characteristics of nondegradable PEGs with similar molecular weights, but they can be metabolized after the cleavage of ester bonds.