Nanocarrier Design and Evaluation of Luliconazole-Loaded SLNs for Enhanced Corneal Penetration and Prolonged Antifungal Action in Fungal Keratitis

Background: Fungal keratitis is a debilitating ocular infection that poses significant treatment challenges due to poor drug retention and limited permeability across the cornea. Solid Lipid Nanoparticles (SLNs) present a promising solution in ocular nanomedicine, offering prolonged drug release, enhanced corneal uptake, and improved therapeutic outcomes. Aim: The aim of this study was to formulate and optimize Luliconazole-loaded Solid Lipid Nanoparticles (LLCZ-SLNs) as a precision nanocarrier system to overcome the challenges of poor corneal permeability and limited drug retention in the treatment of fungal keratitis. Objective: The objective was to develop LLCZ-SLNs using glyceryl monostearate (GMS) and evaluate their physicochemical properties, release kinetics, ex vivo permeation, sterility, isotonicity, irritation potential, and histological safety for ophthalmic use. Method: LLCZ-SLNs were developed through solvent evaporation followed by probe sonication. A 3² full factorial design was employed, using lipid concentration and sonication time as independent variables, to optimize particle size (Ps) and entrapment efficiency (EE). The optimized formulation was characterized for Ps, EE, PDI, ZP, TEM morphology, pH, drug content, in vitro release kinetics, ex vivo permeation, sterility, isotonicity, ocular irritancy (HET-CAM assay), and corneal histopathology. Results: The optimized SLNs exhibited a mean particle size of 124.3 nm, a high EE of 92.3%, a narrow PDI of 0.200, and a stable ZP of -26.9 mV. The formulation maintained a physiological pH of 7.4 ± 0.1 and demonstrated sustained drug release of 73.66 ± 0.34% over 8 hours, following Higuchi kinetics. Ocular biocompatibility was confirmed through sterility and isotonicity assessments, while the HET-CAM assay and histopathological analyses validated the formulation's non-irritant and non-toxic nature. Conclusion: LLCZ-SLNs represent a promising ocular nanocarrier system, facilitating enhanced corneal penetration, sustained antifungal release, and excellent biocompatibility. This formulation addresses critical limitations of conventional treatments for fungal keratitis.