Optimized polymeric micellar In situ gel formulation incorporating luliconazole for targeted management of fungal endophthalmitis: In vitro characterization, ex vivo ocular permeation, and in vivo ocular irritation evaluation.

Abstract

Topical ophthalmic formulations are preferred due to their non-invasive nature and patient compliance but are ineffective for posterior ocular segment diseases like fungal endophthalmitis due to limited drug penetration across ocular barriers. Luliconazole (LCZ), a broad-spectrum imidazole antifungal drug, has shown significant efficacy against major pathogens associated with fungal endophthalmitis; nevertheless, its therapeutic potential is limited because of low aqueous solubility. This study aimed to develop LCZ-loaded polymeric micellar system using Pluronic F127 and F68, optimized via Box-Behnken Design to enhance LCZ solubility by encapsulating it within the micelle hydrophobic core. The optimized micellar formulation had a uniform spherical morphology, with a high entrapment efficiency (86.67 ± 5.24 %), small micellar size (87.34 ± 10.43 nm), PDI (0.669 ± 0.072), and suitable zeta potential (-5.93 ± 2.32 mV). Further, a pH-sensitive in situ gel was formulated by dispersing Carbopol 934 into the optimized micellar dispersion. Both the micellar and in situ gel formulations demonstrated superior release and permeation profiles compared to LCZ-suspension, with at least three months of stability. Rheological analysis of the in situ gel confirmed appropriate gelation and viscosity. Antifungal studies indicated significant efficacy against pathogenic fungi, while in vivo ocular irritation tests in rabbits showed good tolerance. In conclusion, the obtained results suggested that developed polymeric micellar in situ gel can serve as a promising drug delivery system to enhance LCZ ocular antifungal activity.