Electrostatic-tailored Leciplex system of ketoconazole for boosted ocular pharmacology and cytotoxicity assessment

The current study aims to assess efficacy of cationic nano-vesicles, i.e. Leciplex to deliver ketoconazole into ocular surface for management of fungal infection. This research signifies influence of topical ketoconazole on fungal infection. KTN-Leciplex was fabricated by using Lipoid S 100, a cationic surface-active agent such as DDAB and a biocompatible solvent like Transcutol HP using one-step mixing procedure at 70 °C. Self-assembled lipid and cationic surfactant micelles successfully entrap KTN within their unilamellar vesicles. This fabricated KTN-Leciplex was optimized by Box-Behnken design using 3 centre points and assessed for its particle size, polydispersiblity, zeta potential, TEM, entrapment efficiency, mucoadhesion property, antifungal activity on Candida albicans (MTCC 854), cytotoxicity studies on SIRC cell lines (CCL 60-ATCC), HET-CAM test for ocular irritation, in vitro testing of drug release through dialysis membrane sac, ex vivo testing of drug permeation, ex vivo testing of corneal drug retention and histological assessment in comparison with KTN-solution on isolated goat cornea. Optimized KTN-Leciplex has a particle size of 170.5 ± 0.82 nm with a PDI value of 0.163, a zeta potential of 44.6 ± 0.36 mV, TEM images confirmed spherical-shaped nanosized (< 200 nm) vesicles and an entrapment efficiency of 91.86 ± 0.55%; statistical analysis of the mucoadhesion study identified significant change in zeta potential upon interaction with Mucin solution, suggesting possible enhanced ocular residence. The zone of inhibition for Candida albicans was found to be 24.12 ± 0.97 mm. Cytotoxicity in the SIRC (CCL 60-ATCC) cell line shows more than 76.14% of cell viability at all concentration of KTN-Leciplex with IC₅₀ > 1000 µg/ml. HET-CAM studies of KTN-Leciplex confirmed the safety on ocular administration. The drug release study indicates a diffusion barrier with controlled and sustained approach for 10 h. This research confirmed enhanced transcorneal permeation and drug retention in comparison with the KTN-solution. Histological images confirmed no alteration of corneal tissue, disclosing safety on ocular administration. The ketoconazole-loaded Leciplex carries positive charge, which binds with an anionically charged corneal surface. This phenomenon increased the permeation and retention of ketoconazole in the cornea. The ketoconazole delivered through Leciplex can be used to manage ocular fungal infection, such as fungal keratitis.