Antibiotic nanozyme hydrogel depot for single-injection MDR bacterial keratitis therapy via localized antibacterial, pro-healing and corneal reinforcement

Bacterial keratitis (BK), a severe ocular infection caused by pathogenic bacterial invasion, requires urgent therapeutic development due to the limitations of conventional antibiotics, such as drug resistance and systemic toxicity caused by frequent dosing. To address these challenges, we developed an injectable antibiotic nanozyme hydrogel depot (ANHD) for single-dose therapy of BK. The ANHD was prepared by synthesizing the Ce-gatifloxacin nanozyme (CGN, ∼1.26 nm) through metal-organic coordination between cerium nitrate and gatifloxacin, followed by co-precipitation, and subsequently incorporating CGN into an injectable xanthan-PEG hydrogel constructed <i>via</i> Schiff base linkages. The resulting hierarchical composite exhibited multiple functional synergistic effects, including antibacterial activity, reactive oxygen species (O₂ ^·-/H₂O₂/·OH) scavenging activity, promotion of corneal wound healing, and reinforcement of corneal mechanical strength. Furthermore, nanozymes and hydrogels were ubiquitous in the corneal stroma and could exert their functions without penetration across the corneal surface, which distinguished them from the eye drop formulations. In a murine model, single injection of ANHD into corneal stroma effectively treated multidrug-resistant <i>Staphylococcus epidermidis</i> keratitis, with complete bacterial eradication, significant inflammation reduction, and accelerated epithelial repair. These results demonstrated the potential of ANHD in the treatment of ocular infectious diseases.