Nanovesicular Spanlastics Thermosensitive Gel for the Ocular Delivery of Voriconazole: Development, Ex Vivo Transcorneal Permeability, and In Vivo Evaluation in a Rabbit Model of Fungal Keratitis.

Fungal keratitis remains a leading cause of corneal blindness and eye loss worldwide. Conventional antifungal preparations such as those of voriconazole (VCZ) are often limited by rapid precorneal drug loss and poor corneal penetration, leading to suboptimal therapeutic outcomes. This study aimed to address these limitations and improve VCZ antifungal efficacy by incorporating it into nanovesicular spanlastics embedded within a thermosensitive Pluronic F127 gel. VCZ-loaded spanlastics were optimized using a multilevel categoric design and evaluated for VCZ entrapment efficiency (EE%), vesicle size (VS), polydispersity index (PDI), and zeta potential (ZP). The optimized formulation was embedded in Pluronic F127 gel, which was evaluated for gelation temperature, rheological properties, drug release, in vitro antifungal efficacy, ex vivo transcorneal permeability, and in vivo efficacy in a rabbit fungal keratitis (FK) model. The optimized formulation exhibited EE% of 95.91 ± 0.03%, VS of 91.32 ± 0.60 nm, PDI of 0.33 ± 0.03, and ZP of -34.90 ± 1.76 mV. VCZ spanlastics gel exhibited suitable gelation temperature, pH value, and spreadability. It also sustained VCZ release, improved its antifungal efficacy against A. flavus, and showed approximately five-fold higher transcorneal permeability compared with VCZ suspension. In vivo, the VCZ spanlastics gel demonstrated marked resolution of conjunctival redness absence of periocular discharge, and lower levels of the inflammatory marker CD8 compared with the VCZ suspension. These findings confirm the ability of VCZ spanlastics gel to overcome its limitations and highlight its promising potential as an effective topical ocular delivery system for the management of fungal keratitis.