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. 2023 Oct 27;15(11):2537.
doi: 10.3390/pharmaceutics15112537.

Novel Transethosomal Gel Containing Miconazole Nitrate; Development, Characterization, and Enhanced Antifungal Activity

Zara Asghar  1 , Talha Jamshaid  1 , Muhammad Sajid-Ur-Rehman  1 , Usama Jamshaid  2 , Heba A Gad  3   4
Affiliations

Novel Transethosomal Gel Containing Miconazole Nitrate; Development, Characterization, and Enhanced Antifungal Activity

Zara Asghar et al. Pharmaceutics. .

Abstract

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.

Keywords: carbopol 934; ex vivo permeation; gel; health care; in vitro antifungal activity; miconazole nitrate; skin irritation test; transethosomes.

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Conflict of interest statement

The authors state they have no conflict of interest.

Figures

Figure 1
Figure 1
SEM images of optimized MT-8 formulation at 5 µm (A) and 10 µm (B).
Figure 2
Figure 2
FTIR spectra of MCNR (A), lecithin (B), oleic acid (C), and optimized formulation MT-8 (D).
Figure 3
Figure 3
DSC thermograms of MCNR (A), lecithin (B), oleic acid (C), and optimized formulation (D).
Figure 4
Figure 4
pH of MNTG (A) and MNPG (B) at various storage temperatures for 90 days. Two-way ANOVA and paired sample t-test at confidence interval of 95% showed significant differences (p < 0.0001) at different storage temperatures.
Figure 4
Figure 4
pH of MNTG (A) and MNPG (B) at various storage temperatures for 90 days. Two-way ANOVA and paired sample t-test at confidence interval of 95% showed significant differences (p < 0.0001) at different storage temperatures.
Figure 5
Figure 5
Conductivity of MNTG (A) and MNPG (B) at various storage temperatures for 90 days. Two-way ANOVA and paired sample t-test at confidence interval of 95% showed significant differences (p < 0.0016) at different storage temperatures.
Figure 5
Figure 5
Conductivity of MNTG (A) and MNPG (B) at various storage temperatures for 90 days. Two-way ANOVA and paired sample t-test at confidence interval of 95% showed significant differences (p < 0.0016) at different storage temperatures.
Figure 6
Figure 6
Viscosity analysis of freshly prepared MNTG and MNPG at 25 °C (room temperature) (A), optimized MNTG after 3 months (B), and MNPG after 3 months (C), at various storage temperatures (8 °C, 25 °C, 40 °C, 40 °C ± 75% RH). Two-way ANOVA and paired sample t-test at confidence interval of 95% showed significant differences (p < 0.0001) at different storage temperatures.
Figure 7
Figure 7
Spreadability of MNTG (A) and MNPG (B) at various storage temperatures for a time interval of 90 days. Two-way ANOVA and paired sample t-test at confidence interval of 95% showed significant differences (p < 0.0001) at different storage temperatures.
Figure 8
Figure 8
In vitro drug release pattern of MCNR solution (MCNR-SOL), MCNR transethosomal formulation (MT-8), optimized transethosomal gel (MNTG), and MCNR plain gel (MNPG) at pH 5.5 (human skin pH) for a time duration of 24 h.
Figure 9
Figure 9
% drug permeation comparison of optimized transethosomal gel (MNTG) and MCNR plain gel (MNPG) at pH 5.5 (human skin-like) (A) and at pH 7.4 (human blood-like) (B) for a time duration of 24 h. Significant outcomes were obtained (p < 0.0001).
Figure 9
Figure 9
% drug permeation comparison of optimized transethosomal gel (MNTG) and MCNR plain gel (MNPG) at pH 5.5 (human skin-like) (A) and at pH 7.4 (human blood-like) (B) for a time duration of 24 h. Significant outcomes were obtained (p < 0.0001).
Figure 10
Figure 10
In vitro antifungal activity assessment of MCNR plain gel (MNPG), (a) prepared MCNR transethosomal gel (MNTG), (b) marketed product (Daktarin® cream 2%), (c) exhibiting zone of inhibition against standard drug (Fluconazole).
Figure 11
Figure 11
In vivo skin irritation test after MCNR plain gel (MNPG), (Group I), MCNR transethosomal gel (MNTG), (Group II), and marketed cream, (Group III).
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