Formulation design using ionic liquids to enhance luliconazole topical efficacy against superficial Candida albicans...

Superficial fungal infections, such as tinea and ringworm, are challenging to treat due to the poor skin penetration and limited solubility of antifungal agents like luliconazole (LCZ). In this study, we developed a thymol-menthol-based ionic liquid (1:1 molar ratio) to enhance the solubility, topical delivery, and therapeutic performance of LCZ. The LCZ-loaded IL was incorporated into a Carbopol gel and evaluated for in vitro release, ex vivo skin permeability and retention, cytocompatibility, skin irritation, and antifungal activity. The LCZ-IL-gel showed markedly improved in vitro drug release 87.94%, which was markedly higher than that of the LCZ-gel (51.60%) and LCZ-suspension (43.79%). In case of ex vivo skin permeation (75.02%) compared to the free drug suspension (42.96% and 28.21%, respectively), while remaining non-irritant and cytocompatible. Altogether, LCZ-IL-gel showed a 4.8-fold (20.93%) increase in skin retention compared to the free suspension. It also demonstrated superior antifungal activity against Candida albicans compared to that of marketed formulations. The improved permeation and antifungal activity of LCZ-IL-gel indicate its strong potential for clinical translation as a more effective topical therapy for superficial fungal infections.