High Molecular Weight Biodegradable Poly(ethylene glycol) via Carboxyl-Ester Transesterification

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.