Antifungal Efficacy of Luliconazole-Loaded Nanostructured Lipid-Carrier Gel in an Animal Model of Dermatophytosis

<b>Background:</b><i>Trichophyton indotineae</i> terbinafine-resistant infections are emerging in healthy individuals. Luliconazole, an imidazole antifungal that is effective against skin infections, faces challenges due to low water solubility and poor skin penetration. This study aimed to formulate a luliconazole-loaded nanostructured lipid-carrier (NLC) gel in a Carbopol-based system to enhance drug absorption and efficacy in a guinea pig model of dermatophytosis. <b>Methods</b>: Luliconazole-loaded nanostructured lipid carriers (NLCs) were prepared using a solvent evaporation method and gel formulation. Skin absorption and retention were assessed via Franz diffusion cells. The antifungal efficacy was tested against <i>T. indotineae</i> in thirty guinea pigs with induced tinea corporis, divided into five treatment groups. Mycological, clinical, and histopathological evaluations were conducted, along with skin irritation studies for safety. <b>Results</b>: LCZ-NLC demonstrated significantly better skin penetration than simple luliconazole gel, with cumulative drug penetration of 71.8 ± 3.7 μg/cm² versus 50.9 ± 4.2 μg/cm² after 24 h. Both formulations achieved complete infection resolution after 21 and 28 days, with reduced inflammation and no local irritations. On day 21, the LCZ-NLC 1% gel significantly reduced lesion scores and mycological evidence of infection compared to the terbinafine-treated groups, untreated controls, and NLC-gel-treated group (<i>p</i> < 0.05). Histopathological analysis indicated a reduction in both epidermal thickening and fungal burden in the models that received treatment with the LCZ-NLC 1% gel. <b>Conclusions</b>: Luliconazole-loaded lipid carriers enhance drug absorption and efficacy, suggesting shorter treatment durations and improved patient outcomes for resistant fungal infections. However, further studies are warranted to correlate these findings with clinical outcomes.