Synthesis, properties, and applications of a polyampholyte hydroxypropyl chitosan derivative with the phenylboronic acid functional group

Abstract

Phenylboronic acid (PBA) groups are effective in building glucose-responsive drug delivery systems. Chitosan (CS) offers distinct advantages in the construction of PBA-based biomaterials, such as biodegradability and biocompatibility. However, challenges still persist due to the limited solubility of CS. This study proposes an efficient approach to introduce PBA groups into CS chains within 1 h via the O-(7-azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (HATU)-mediated amidation between 3-carboxyphenylboronic acid (CPBA) and O-hydroxypropyl chitosan (HPCS). The results showed that a wide range of substitution degrees, from 0.15 to 0.78, could be finely controlled by the amount of CPBA added. Furthermore, the obtained novel carboxyphenylboronic acid-grafted hydroxypropyl chitosan (PBA-HPCS) derivative showed enhanced crystallinity and thermostability compared to HPCS, and it demonstrated solubility in an alkaline solution. Based on the reversible bonding between the boronic acid group and cis-1,2/1,3-diols, PBA-HPCS was successfully used as an efficient crosslinker for the preparation of hydrogels incorporating sorbitol and polyhydroxy polymers, such as guar gum and polyvinyl alcohol. These hydrogels exhibited rapid gelation, rapid self-healing, injectability, and responsiveness to glucose and pH. These findings suggest that PBA-HPCS holds promise for advancing the development of PBA-based biomaterials.

Keywords: Hydroxypropyl chitosan; Phenylboronic acid; Self-healing hydrogel.