Phenylboronic Acid Functionalized Polycarbonate Hydrogels for Controlled Release of Polymyxin B in Pseudomonas Aeruginosa Infected Burn Wounds

Abstract

While physically crosslinked polycarbonate hydrogels are effective drug delivery platforms, their hydrophobic nature and lack of side chain functionality or affinity ligands for controlled release of hydrophilic drugs underscore the importance of their chemical compositions. This study evaluates an array of anionic hydrogel systems of phenylboronic acid functionalized triblock copolymers prepared via reversible physical interactions. Variation of key chemical functionalities while maintaining similar core structural features demonstrates the influence of the substitution position and protection of the boronic acid functionality on gel viscoelasticity and mechanical strength at physiological pH. The optimum gel systems obtained from the meta-substituted copolymers (m-PAP) are stable at physiological pH and nontoxic to mammalian dermal cells. The polymyxin B loaded m-PAP hydrogels demonstrate controlled in vitro drug release kinetics and in vitro antimicrobial activity against Pseudomonas aeruginosa over 48 h. In vivo antimicrobial efficacy of the drug loaded hydrogels further corroborates the in vitro results, demonstrating sustained antimicrobial activity against P. aeruginosa burn wound infections. The current strategy described in this study demonstrates a straightforward approach in designing physiologically relevant boronic acid hydrogel systems for controlled release of cationic antimicrobials for future clinical applications.

A physiologically stable hydrogel formulation from a meta-substituted phenylboronic acid functionalized "ABA" triblock copolymer controls the release of polymyxin B via noncovalent matrix–drug interactions between the anionic polymer ligands and the cationic peptide. The biocompatible hydrogel demonstrates sustained in vitro and in vivo antimicrobial efficacy, against topical burn wound infections caused by Pseudomonas aeruginosa.

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