Formulation and evaluation of flucytosine-loaded nanoemulgel for enhanced antifungal activity through in vitro and in vivo studies

Background: Fungal skin infections constitute a prevalent global health issue, accompanied by increasing resistance to traditional antifungal medications. Flucytosine, a pyrimidine analogue exhibiting potent antifungal properties, is constrained in topical use due to inadequate skin absorption and fast elimination. Nanoemulgels, which integrate nanoemulsions with gels, enhance solubility, penetration, stability, and prolonged release, representing a viable approach for topical antifungal administration. Methods: The nanoemulgel was prepared utilizing Carbopol 940 as the gelling agent. The formulations (NEG1–NEG8) were evaluated for physical appearance, pH, viscosity, spreadability, drug content, and in vitro drug release and release kinetics. Antifungal activity was assessed by zone-of-inhibition assays and in vivo using Wistar rats infected with Candida albicans. Skin irritation, histopathology, and a three-month stability study were also conducted. Result and Discussion: The improved NEG5 formulation had a favorable pH (5.92±0.03), high drug content (95.3±1.83%), and maximum cumulative drug release (92.97±5.91% at 24 hours) with first-order release kinetics (R2= 0.9959). The commercial luliconazole cream and NEG5 showed increased antifungal effectiveness in vivo, with lesion clearance by Day 14. The histopathology showed tissue repair with minimal inflammation. NEG5 surpassed other formulations in zone-of-inhibition assays for antifungal activity. No skin irritation was reported, and the formulation was stable for three months under various storage conditions. The improved physicochemical and therapeutic performance of NEG5 suggests enhanced skin penetration and sustained drug release, addressing the limitations of conventional flucytosine therapies. Conclusion: Flucytosine-loaded nanoemulgel (NEG5) offers a promising, effective topical treatment for fungal skin infections with improved drug delivery and patient safety.