Formulation, Pharmacokinetics, and In Vivo Antifungal Activity of a Novel Topical Nanostructured Lipid Carrier of Fluconazole for Vulvovaginal Candidiasis Management in Nigeria

Background: Vulvovaginal candidiasis (VVC) is among the most common fungal infections in Nigerian women, with recurrent forms affecting a significant proportion of the reproductive age population. Conventional oral and topical fluconazole formulations face challenges including systemic side effects, increasing resistance, and poor vaginal drug retention. Nanostructured lipid carriers (NLCs) offer superior drug loading, controlled release, and mucoadhesive properties for vaginal drug delivery. This study develops and characterises an NLC-based fluconazole vaginal gel optimised for VVC management. Methods: NLCs were prepared by melt-emulsification using Compritol and Miglyol with Poloxamer 407 stabiliser. Formulation optimisation employed a Box-Behnken design. Characterisation included particle size, entrapment efficiency, in vitro release, and rheological profiling. Pharmacokinetics of the NLC vaginal gel were assessed in female Wistar rats and compared to conventional fluconazole gel. In vivo antifungal efficacy was evaluated using a rat model of Candida albicans vaginal infection. Results: Optimised NLCs showed particle size of 212 nm, entrapment efficiency of 84 percent, and biphasic release over 72 hours. Vaginal tissue drug concentrations with NLC gel were threefold higher than conventional gel, while plasma levels were significantly lower, indicating localised delivery. In vivo fungal load reduction was significantly superior for NLC gel (p less than 0.001). Conclusion: NLC-based fluconazole vaginal gel demonstrates superior local pharmacokinetics and antifungal activity, offering a promising formulation advancement for VVC management in Nigerian women. Keywords: nanostructured lipid carriers, fluconazole, vaginal candidiasis, drug delivery, pharmacokinetics