A comprehensive review on recent nanosystems for enhancing antifungal activity of fenticonazole nitrate from different routes of administration

Abstract

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.

Keywords:

• Fenticonazole Nitrate
• terpesomes
• olaminosomes
• confidence interval and docking study

Disclosure statement

No potential conflict of interest was reported by the authors.

Ethical approval statement

All the studied nanosystems had received an ethical approval for their ex vivo and in vivo studies. The ocular nanosystems (O-NV, O-OLN and O-TP) used adult male albino rabbits, having an average body weight of 2 ± 0.5 kg and caged individually at 25 ± 2 °C, with 12 hours cycle alternating of light and dark. Standard commercial food and tap water were supplied to the animals. Rabbits’ eyes were initially examined in order to select only animals with no signs of ocular inflammation. When required, anesthesia was done by intramuscular injection of 35 mg/kg ketamine and 5 mg/kg xylazine followed by decapitation (Elsayed & Sayed, 2017; Eldeeb Salah & Ghorab, 2019). Research Ethics Committee (REC), Faculty of Pharmacy, Cairo University approved their study (approval number PI 3132 for O-NV and O-OLN MIC2672 for O-TP) according to the local and national regulatory standards set for animal care (Albash et al., 2021; Ahmed et al., 2022a,b). V-TP studies were certified by Faculty of Pharmacy, Damanhour University (approval number 720PM16) for using Sprague Dawley rats, weighing 200–250 gm. However, Research Ethics Committee (REC), Faculty of Pharmacy, Cairo University (in compliance with the EU directive 2010/63/EU for animal experiment) certified T-CE studies using male Wistar rats, weighing 150–200 gm, with an average age of 7 weeks. The rats were housed in cages at 22 ± 1 °C and 50–55% humidity under a 12 hours cycle alternating of light and dark with regular suppling of commercial food and tap water (Albash et al., 2020; 2021). The use of animals for ex vivo or in vivo studies provides a clear indication of the expected activity of the studied nanosystems inside the human body. Regarding T-T-NV, the Institutional Review Board, Faculty of Medicine, Minia University had reviewed and approved the clinical studies (approval number 41:5/2021) (Albash et al., 2022). All the human participants provided informed consent prior to taking part. All figures had received copyright permission from the corresponding authors. Moreover, the studied formulae were published as open access articles distributed under the terms of the Creative Commons CC BY license, which permits unrestricted use, distribution, reproduction in any medium, provided the original work is properly cited.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.