Self-disinfecting adhesive chitosan nanospray therapeutics for on-demand antibiotic prophylaxis against healthcare-associated infections

Healthcare-associated infections (HAIs) present a critical clinical challenge that significantly increases patient morbidity and healthcare costs. While pH-responsive antibacterial nanoparticles (NPs) have emerged as promising therapeutic platforms, current strategies are hampered by poor tissue adhesion and premature drug release under physiological conditions. Here, we propose sprayable adhesive antibacterial NPs based on catechol-conjugated chitosan with dynamic Cu²⁺ coordination for infection-triggered vancomycin release in HAI prevention. This multifunctional therapeutic system uniquely integrates robust tissue adhesion, infection-responsive drug release, superior biocompatibility, and potent antibacterial activity unlike conventional approaches that address individual aspects separately. The catechol-Cu²⁺ coordinated chitosan NPs (Cat-CS@Van NPs) fabricated via electrospraying exhibited superior mucoadhesive properties through multiple interaction mechanisms. Crucially, vancomycin release at acidic pH (5.0) was ∼2.7-fold higher than at physiological pH (7.4), achieving ∼75.5 % release within 8 h through acidification-induced destabilization of catechol-Cu²⁺ complexes. The Cat-CS@Van NPs also retained excellent sprayability without structural degradation and maintained strong tissue adhesion after washing. In vitro and ex vivo assays showed broad-spectrum antibacterial activity against both Gram-positive and Gram-negative bacteria, enabling complete bacterial eradication at the minimum inhibitory loading concentration and effective prevention of bacterial translocation across medical device interfaces. Furthermore, in vivo wound infection models demonstrated improved therapeutic outcomes with enhanced wound healing compared to controls. Thus, our sprayable Cat-CS@Van NP system provides a promising approach for site-directed antibacterial prophylaxis to achieve instant and sustainable bactericidal action for effective HAI prevention.