Ultra-deformable liposomes containing terpenes (terpesomes) loaded fenticonazole nitrate for treatment of vaginal candidiasis: Box-Behnken design optimization, comparative <i>ex vivo</i> and <i>in vivo</i> studies

Abstract

Fenticonazole nitrate (FTN) is a potent antifungal drug adopted in the treatment of vaginal candidiasis. It has inadequate aqueous solubility hence, novel ultra-deformable liposomes 'Terpesomes' (TPs) were developed that might prevail over FTN poor solubility besides TPs might abstain the obstacles of mucus invasion. TPs were assembled by thin-film hydration then optimized by Box Behnken design utilizing terpenes ratio (X₁), sodium deoxycholate amount (X₂), and ethanol concentration (X₃) as independent variable, whereas their impact was inspected for entrapment efficiency (Y₁), particle size (Y₂), and polydispersity index (Y₃). Design Expert^® was bestowed to select the optimal TP for more studies. The optimal TP had entrapment efficiency of 62.18 ± 1.39%, particle size of 310.00 ± 8.16 nm, polydispersity index of 0.20 ± 0.10, and zeta potential of -10.19 ± 0.2.00 mV. Elasticity results were greater in the optimal TP related to classical bilosomes. Further, <i>ex vivo</i> permeation illustrated tremendous permeability from the optimal TP correlated to classical bilosomes, and FTN suspension. Besides, <i>in vivo</i> assessment displayed significant inhibition effect in rats from FTN-TPs gel compared to FTN gel. The antifungal potency with undermost histopathological variation was detected in rats treated with FTN-TPs gel. Overall, the acquired findings verified the potency of utilizing FTN-TPs gel for treatment of vaginal candidiasis.