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

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.