RESUMO
Miconazole nitrate (MCNR), an antifungal drug, is used to treat superficial infections. The objective of the current study was to assess the antifungal effectiveness of MCNR-loaded transethosomal gel (MNTG) against Candida albicans in an in vivo rat model. The outcomes were compared with those of the miconazole nitrate gel (MNG) and marketed Daktarin® cream (2%) based on histopathological and hematological studies. The results of the skin irritation test revealed the safety profile of the MNTG. The MNTG demonstrated the greatest antifungal activity in the histological analysis and the visible restoration of the skin, and the rats revealed an apparent evidence of recovery. Compared to the untreated group, the treated group's lymphocyte and white blood cells counts increased, but their eosinophil counts decreased. In conclusion, MNTG exhibited the greatest antifungal activity, which might be connected to the improved skin permeability of the transethosome's nanosized vesicles. Therefore, it could be considered a promising carrier for topical usage and the treatment of cutaneous candidiasis. More clinical research needs to be performed in order to demonstrate its effectiveness and safe usage in humans.
RESUMO
Miconazole nitrate (MCNR) is a BCS class II antifungal drug with poor water solubility. Although numerous attempts have been made to increase its solubility, formulation researchers struggle with this significant issue. Transethosomes are promising novel nanocarriers for improving the solubility and penetration of drugs that are inadequately soluble and permeable. Thus, the objective of this study was to develop MCNR-loaded transethosomal gel in order to enhance skin permeation and antifungal activity. MCNR-loaded transethosomes (MCNR-TEs) were generated using the thin film hydration method and evaluated for their zeta potential, particle size, polydispersity index, and entrapment efficiency (EE%). SEM, FTIR, and DSC analyses were also done to characterize the optimized formulation of MCNR-TEs (MT-8). The optimized formulation of MCNR-TEs was incorporated into a carbopol 934 gel base to form transethosomal gel (MNTG) that was subjected to ex vivo permeation and drug release studies. In vitro antifungal activity was carried out against Candida albicans through the cup plate technique. An in vivo skin irritation test was also performed on Wistar albino rats. MT-8 displayed smooth spherical transethosomal nanoparticles with the highest EE% (89.93 ± 1.32%), lowest particle size (139.3 ± 1.14 nm), polydispersity index (0.188 ± 0.05), and zeta potential (-18.1 ± 0.10 mV). The release profile of MT-8 displayed an initial burst followed by sustained release, and the release data were best fitted with the Korsmeyer-Peppas model. MCNR-loaded transethosomal gel was stable and showed a non-Newtonian flow. It was found that ex vivo drug permeation of MNTG was 48.76%, which was significantly higher than that of MNPG (plain gel) (p ≤ 0.05) following a 24-h permeation study. The prepared MCNR transethosomal gel exhibited increased antifungal activity, and its safety was proven by the results of an in vivo skin irritation test. Therefore, the developed transethosomal gel can be a proficient drug delivery system via a topical route with enhanced antifungal activity and skin permeability.
