Design and Evaluation of Econazole-Loaded Nanostructured Lipid Carriers for Ocular Treatment of Fungal Keratitis: In vitro and Ex vivo Studies

Background: Fungal keratitis (FK) is a major cause of eye morbidity and monocular blindness, particularly in humid climates. Ocular drug delivery is challenging due to anatomical barriers, tear flow, and nasal drainage, which reduce corneal penetration and decrease bioavailability. Conventional antifungal treatments often lack efficacy for deep keratitis. In order to address these limitations, this study explores encapsulating econazole into nanostructured lipid carriers (NLCs). Objective: To optimize, develop, and characterize econazole-loaded NLCs for ocular drug delivery. Methods: NLCs were prepared using a modified pre-emulsification and probe sonication technique with stearic acid as the solid lipid and oleic acid as the liquid lipid. The resulting nano-emulsion was homogenized, cooled, and incorporated into a Carbopol 940-based gel. Optimization was performed using JMP software. Results: Optimised NLCs exhibited a particle size of 192.3 nm, a PDI of 0.207, and a zeta potential of -44.8, indicating stability. Drug content was 85.18% in NLCs and 83.8% in the gel, with an entrapment efficiency of 66.9%. Ex vivo studies showed 84.51% drug permeation from the gel over 17 hours compared to 89.37% in 12 hours from conventional formulations. Permeation data obtained from the ex vivo study revealed the steady-state flux (Jss) to be 88.53 μg/cm²/hr, the permeability coefficient 0.0216 cm/hr, and the diffusion coefficient 0.00325 cm²/hr. Drug release followed zeroorder kinetics with anomalous transport. Stability testing confirmed the gel’s stability for three months. Conclusion: The econazole-loaded NLC gel enhanced ocular retention, bioavailability, and sustained release, offering a promising treatment for FK.