Naturally derived mucoadhesive nanosuspension for treatment of multiple staged ocular infections

Bacterial ocular infections pose significant risks to vision and incur substantial economic burdens worldwide. Current standards of care, such as eye drops and ointments, suffer from poor drug bioavailability (<5 %), rapid clearance, and insufficient retention, preventing dual prophylactic and therapeutic efficacy. To address these limitations, we developed naturally derived mucoadhesive gelatin methacryloyl (GelMA) nanoparticles (NPs) functionalized with phenylboronic acid (PBA), named GelMAP, for the sustained delivery of moxifloxacin (MFX), a broad-spectrum antibacterial agent. Dispersed in a custom-designed shear-thinning matrix formulated with hyaluronic acid (HA) to enhance viscosity and ocular retention, the GelMAP nanosuspension exhibited robust mucoadhesion, efficient drug loading (>70 %), and sustained in vitro drug release. Biocompatibility and bactericidal efficacy were confirmed in vitro, showing >95 % cell viability in NIH 3T3 and human corneal epithelial cells, along with notable antibacterial activity against key ocular pathogens over 7 days. In a healthy murine model, the biosafety of the nanosuspension was confirmed. The MFX-loaded nanosuspension demonstrated around 2.6-fold longer half-life in the cornea compared to commercial MFX drops (Vigamox®), indicating higher drug retention. Designed to prevent infection and treat established conditions, its efficacy was evaluated in a murine bacterial keratitis model. The MFX-loaded nanosuspension outperformed Vigamox® by reducing corneal opacity, achieving lower clinical scores (indicating better outcomes), and decreasing bacterial counts. Histological analysis showed minimal inflammation and a preserved corneal structure, validating the effectiveness of the GelMAP nanosuspension. Currently, no NP formulation has been widely demonstrated to offer dual efficacy in both early and established infections, underscoring GelMAP nanosuspension's potential for comprehensive ocular infection management by reducing treatment frequency, minimizing complications, and enhancing patient compliance.