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.

The purpose of this manuscript was to develop and optimize Fenticonazole Nitrate (FTN)-loaded novasomes aiming to enhance drug corneal penetration and to improve its antifungal activity. Ethanol injection was used to formulate FTN-loaded novasomes adopting a central composite design. The researched factors were: stearic acid concentration (g%) (A), span 80: drug ratio (B) and cholesterol amount (mg) (C), and their effects on percent entrapment efficiency (EE%), particle size (PS), poly-dispersity index (PDI), zeta potential (ZP), and in vitro drug release after 8 hours (Q8h) were studied. Numerical optimization by Design-Expert® software was employed to select the optimum formula in respect to highest EE%, ZP (as absolute value), and Q8h >80% and lowest PS and PDI. Additional evaluation of the optimum formula was accomplished by short term stability study, effect of gamma sterilization, determination of Minimal Inhibitory Concentration and ex vivo corneal permeation study. The in vivo evaluation of the optimum formula was done to ensure its safety via in vivo ocular irritancy and in vivo corneal tolerance studies. Also, the efficacy was confirmed through in vivo corneal uptake study and susceptibility test. The optimum formula with the highest desirability value (0.738) showed EE% (94.31%), PS (197.05 nm), ZP (-66.95 mV) and Q8h (85.33%). It revealed to be safe, with augmented corneal permeation (527.98 µg/cm2) that leads to higher antifungal activity. The above results confirmed the validity of novasomes to improve the corneal permeation and antifungal activity of Fenticonazole Nitrate.

The current investigation aimed for loading fenticonazole nitrate (FTN), an antifungal agent with low aqueous solubility, into trans-novasomes (TNs) for management of tinea corporis topically. TNs contain Brij® as an edge activator besides the components of novasomes (cholesterol, Span 60, and oleic acid) owing to augment the topical delivery of FTN. TNs were fabricated applying ethanol injection method based on D-optimal experiment. TNs were evaluated with regard to entrapment efficiency percent (EE%), particle size (PS), polydispersity index (PDI), and zeta potential (ZP). Further explorations were conducted on the optimum formulation (F7). F7 showed spherical appearance with EE%, PS, PDI, and ZP of 100.00 ± 1.10%, 358.60 ± 10.76 nm, 0.51 ± 0.004, and -30.00 ± 0.80 mV, respectively. The in silico study revealed the ability of the FTN-cholesterol complex to maintain favorable interactions throughout the molecular dynamics simulation (MDS) study. Moreover, Trichophyton mentagrophytes growth was inhibited effectively by F7 than by FTN suspension applying 2,3-bis(2-methyloxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) reduction assay. Furthermore, a clinical appraisal on patients with tinea corporis fungal lesions confirmed the superiority of F7 compared to Miconaz® cream in the magnitude of clinical cure of tinea corporis. Thereby, TNs could be considered as promising vesicles for enhancing the antifungal potential of FTN for the topical management of tinea corporis.

UNASSIGNED: The aim of the current study was to load fenticonazole nitrate, a slightly water-soluble antifungal agent, into terpene-enriched phospholipid vesicles (terpesomes) as a potential delivery system for the management of ocular fungal infection.
UNASSIGNED: Thin film hydration method was used to prepare terpesomes according to a 32 full factorial design to inspect the effect of several variables on vesicles\' features. The investigated factors were terpenes type (X1) and terpenes amount (X2) while the dependent responses were encapsulation efficiency percent (Y1), particle size (Y2) and polydispersity index (Y3). Design Expert® program was used to chose the best achieved formula. The selected terpesomes were further optimized via incorporation of a positive charge inducer (stearylamine) to enhance adhesion to the negatively charged mucus covering the eye surface. The in vivo performance of the optimized fenticonazole nitrate-loaded terpesomes relative to drug suspension was evaluated by measuring the antifungal activity (against Candida albicans) retained in the tear\'s fluid at different time intervals after ocular application in albino rabbits.
UNASSIGNED: The optimized terpesomes showed spherical vesicles with entrapment efficiency of 79.02±2.35%, particle size of 287.25±9.55 nm, polydispersity index of 0.46±0.01 and zeta potential of 36.15±1.06 mV. The in vivo study demonstrated significantly higher ocular retention of the optimized fenticonazole nitrate-loaded terpesomes relative to the drug suspension. Moreover, the histopathological studies proved the safety and biocompatibility of the prepared terpesomes.
UNASSIGNED: The obtained results verified the potential of the terpesomes for safe and effective ocular delivery of fenticonazole nitrate.

In this investigation, we focused on ceramide IIIB, a skin component whose depletion tends to augment multiple skin disorders and fungal infections. Ceramide IIIB was included into PEGylated surfactant-based vesicular phospholipid system to formulate \'PEGylated cerosomes\' (PCs) loaded with fenticonazole nitrate (FTN). FTN is a potent antifungal agent adopted in the treatment of mixed mycotic and bacterial infections. The ceramide content of the vesicles may provide protective and regenerative skin activity whereas Brij®; the PEGylated surfactant, can enhance drug deposition and skin hydration. Both components are expected to augment the topical effect of FTN. PCs were prepared by thin-film hydration technique. A 23 full-factorial design was applied to study the effect of ceramide amount (X1), Brij type (X2) and Brij amount (X3) on the physicochemical properties of the formulated PCs namely; entrapment efficiency (EE%;Y1), particle size (PS;Y2), polydispersity index (PDI;Y3) and zeta potential (ZP;Y4). The optimal formula was selected for further in-vivo dermatokinetic and histopathological study. The optimal FTN-loaded PC (PC6) showed nanosized cerosomes (551.60 nm) with high EE% (83.00%w/w), and an acceptable ZP value of 20.90 mV. Transmission electron micrographs of the optimal formula illustrated intertwined tubulation form deviated from the conventional spherical vesicles. Finally, the dermatokinetic study of PC6 showed higher drug concentration and localization of FTN in skin layers when compared with FTN suspension and the histopathological study confirmed its safety for topical application. The overall findings of our study verified the effectiveness of utilizing PEGylated cerosomes to augment the activity of FTN as a topical antifungal agent.

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, ex vivo permeation illustrated tremendous permeability from the optimal TP correlated to classical bilosomes, and FTN suspension. Besides, in vivo 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.