Development of an Injectable Boronic Ester Nanocomposite Hydrogel for pH- and Thermo-Responsive Gentamicin Delivery and Antibacterial Activity

Abstract

Infected wounds require localized antimicrobial treatment strategies that provide sustained drug release, reduce systemic antibiotic exposure, and promote tissue repair. This study reports an infection-responsive nanocomposite hydrogel platform based on dynamic covalent boronic ester chemistry for triggered topical antibiotic delivery. Phenylboronic acid (PBA)-functionalized cationic nanoparticles (PBA-NPs) were employed as three-dimensional crosslinkers and combined with poly(vinyl alcohol) (PVA) to construct an injectable nanocomposite hydrogel via reversible boronic ester interactions. The nanocomposite hydrogel was characterized for morphology, injectability, rheological properties, stimuli-responsive behavior, in vitro antibiotic release, and antibacterial activity against Staphylococcus aureus and Pseudomonas aeruginosa. The resulting nanocomposite hydrogel exhibited a gel–sol transition at 39.7°C, while the pH-dependent chemistry of the boronic ester network supports enhanced network dissociation under mildly acidic conditions (pH 6.5). This dual pH- and thermo-responsive behavior enabled on-demand release of encapsulated gentamicin sulfate while preserving viscoelastic recovery consistent with dynamic network reconstruction. The cationic PBA-NPs exhibited intrinsic antibacterial activity and generated enhanced antimicrobial effects when combined with gentamicin. Zones of inhibition reached 22 mm (S. aureus) and 25 mm (P. aeruginosa) at 3% drug loading. Collectively, these findings demonstrate that dynamic covalent boronic ester nanocomposite hydrogel represents a promising injectable platform for infection-responsive localized antibiotic delivery and antibacterial wound management.