This review aims to comprehensively highlight the recent nanosystems enclosing Fenticonazole nitrate (FTN) and to compare between them regarding preparation techniques, studied factors and responses. Moreover, the optimum formulae were compared in terms of
in vitro, ex vivo
and
in vivo
studies in order to detect the best formula. FTN is a potent antifungal imidazole compound that had been used for treatment of many dangerous fungal infections affecting eye, skin or vagina. FTN had been incorporated in various innovative nanosystems in the recent years in order to achieve significant recovery such as olaminosomes, novasomes, cerosomes, terpesomes and trans-novasomes. These nanosystems were formulated by various techniques (ethanol injection or thin film hydration) utilizing different statistical designs (Box-Behnken, central composite, full factorial and D-optimal). Different factors were studied in each nanosystem regarding its composition as surfactant concentrations, surfactant type, amount of oleic acid, cholesterol, oleylamine, ceramide, sodium deoxycholate, terpene concentration and ethanol concentration. Numerous responses were studied such as percent entrapment efficiency (EE%), particle size (PS), poly-dispersity index (PDI), zeta potential (ZP), and
in vitro
drug release. Selection of the optimum formula was based on numerical optimization accomplished by Design-Expert® software taking in consideration the largest EE %, ZP (as absolute value) and
in vitro
drug release and lowest PS and PDI.
In vitro
comparisons were done employing different techniques such as Transmission electron microscopy, pH determination, effect of gamma sterilization, elasticity evaluation and docking study. In addition to,
ex vivo
permeation,
in vivo
irritancy test, histopathological, antifungal activity and Kinetic study.