Luliconazole–niacinamide lipid nanocarrier laden gel for enhanced treatment of vaginal candidiasis: in vitro, ex vivo, in silico and preclinical insights

Abstract

A lipid-based nanocarrier system is a novel technique for the delivery of poorly soluble drugs through topical delivery. This study developed a dual-drug (luliconazole: LZ, and niacinamide: NM) loaded lipid nanocarrier (LN)-laden gel for the treatment of vaginal candidiasis. The LNs were prepared using cholesterol and soya-α-lecithin through a thin-film hydration technique. The average vesicle size, polydispersity index, and zeta potential of the optimized LZNMLNs were 126.40 ± 1.30 nm, 0.276, and −34.6 ± 0.8 mV, respectively, and the formulation showed the sustained release of both drugs over an extended period. Selected LZNMLNs were incorporated into a bio-adhesive gel. The optimized LZNMLNs-gel showed excellent viscosity, spreadability, and bio-adhesiveness. The optimized LZNMLNs-gel exhibited significantly higher permeation of LZ (1.46-fold) and NM (1.55-fold) than LZNM gel. The optimized LZNMLNs-gel showed significantly higher in vitro antifungal activity (ZOI = 34 ± 2 mm) than commercial Candid V gel (18 ± 1 mm). The optimized LZNMLNs-gel did not show any cytotoxicity against vaginal epithelial cells. The bioavailability of LZNMLNs-gel was significantly (P < 0.05) increased (1.94-fold for LZ and 1.33-fold for NM) compared to Candid V, with a decrease in total clearance indicating sustained release of the drug, which may lead to the maintenance of therapeutic concentration for an extended period. In vivo antifungal activity showed that the optimized LZNMLNs-gel completely treated the infection on the 7th day of treatment in an induced rabbit model, compared to the commercial gel (Candid V gel, 10 days). Based the findings, it can be concluded that LN-laden gel is an alternative carrier for improvement of the topical delivery of drugs for the treatment of vaginal candidiasis.