Background Miconazole nitrate, a BCS Class II drug (< 3 µg/mL solubility, poor skin permeability), requires enhanced topical delivery systems. Objective Develop optimized transethosomal gel for superior skin penetration and antifungal efficacy against Candida albicans. Methods Cold method preparation, Central Composite Design (CCD) optimization (soy lecithin 2.5–3.5% w/v, ethanol 20–60% v/v; n = 9 formulations). Evaluated vesicle size, entrapment efficiency (EE), zeta potential, Transmission Electron Microscopy (TEM), Fourier Transform Infrared (FTIR) spectroscopy. Carbopol 934 gel incorporation. Assessed In vitro release, ex vivo Franz permeation (cellophane MWCO 12–14 kDa, PBS pH 7.4, 32 °C, 400 rpm; samples: 0.25, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 12, 24 h), antifungal disc diffusion, In vivo irritation (Wistar rats, OECD 404), Confocal Laser Scanning Microscopy (CLSM; Rhodamine B λex 540/λem 630 nm) . Results Optimized F-3: EE 81.56%, vesicle size 360.15 nm (Table 3). Transethosomal gel showed 48.76% permeation vs. plain gel (p < 0.05), inhibition zone 13.50 ± 0.02 mm vs. Micogel® 9.60 mm, dermis penetration via CLSM. Conclusion CCD-optimized transethosomal gel enhances miconazole delivery vs. existing formulations, warranting clinical evaluation. Graphical Abstract Miconazole nitrate was formulated into transethosomes using the cold method with phospholipids, ethanol, and an edge activator to improve skin permeability. Formulation variables (ethanol and soy lecithin concentration) were optimized via Central Composite Design, with entrapment efficiency and vesicle size evaluated through 3D surface plots, and morphology confirmed by TEM. In vitro testing included antifungal activity against Candida albicans (disc diffusion) and drug permeation studies using a Franz diffusion cell. In vivo skin irritation tests were conducted on Wistar rats, while ex vivo penetration was assessed by CLSM using fluorescently labeled gel. The optimized formulation achieved high entrapment efficiency (~ 81.56%), small vesicle size (~ 360.15 nm), and stability, showing a larger inhibition zone than marketed cream, higher 24-hour cumulative drug release, minimal skin irritation, and confirmed deep skin penetration into the epidermis and dermis.

Development and Evaluation of Miconazole Nitrate-Loaded Transethosomal Gel for Enhanced Skin Permeability and Antifungal Efficacy

期刊论文
发表日期：

2026年1月12日

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Naina Dubey,
Seema Sharma,
Manish Mohan Ghadage,
Sampat Singh Tanwar

摘要

Background

Miconazole nitrate, a BCS Class II drug (< 3 µg/mL solubility, poor skin permeability), requires enhanced topical delivery systems.

Objective

Develop optimized transethosomal gel for superior skin penetration and antifungal efficacy against Candida albicans.

Methods

Cold method preparation, Central Composite Design (CCD) optimization (soy lecithin 2.5–3.5% w/v, ethanol 20–60% v/v; n = 9 formulations). Evaluated vesicle size, entrapment efficiency (EE), zeta potential, Transmission Electron Microscopy (TEM), Fourier Transform Infrared (FTIR) spectroscopy. Carbopol 934 gel incorporation. Assessed In vitro release, ex vivo Franz permeation (cellophane MWCO 12–14 kDa, PBS pH 7.4, 32 °C, 400 rpm; samples: 0.25, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 12, 24 h), antifungal disc diffusion, In vivo irritation (Wistar rats, OECD 404), Confocal Laser Scanning Microscopy (CLSM; Rhodamine B λex 540/λem 630 nm) .

Results

Optimized F-3: EE 81.56%, vesicle size 360.15 nm (Table 3). Transethosomal gel showed 48.76% permeation vs. plain gel (p < 0.05), inhibition zone 13.50 ± 0.02 mm vs. Micogel^® 9.60 mm, dermis penetration via CLSM.

Conclusion

CCD-optimized transethosomal gel enhances miconazole delivery vs. existing formulations, warranting clinical evaluation.

Graphical Abstract

Miconazole nitrate was formulated into transethosomes using the cold method with phospholipids, ethanol, and an edge activator to improve skin permeability. Formulation variables (ethanol and soy lecithin concentration) were optimized via Central Composite Design, with entrapment efficiency and vesicle size evaluated through 3D surface plots, and morphology confirmed by TEM. In vitro testing included antifungal activity against Candida albicans (disc diffusion) and drug permeation studies using a Franz diffusion cell. In vivo skin irritation tests were conducted on Wistar rats, while ex vivo penetration was assessed by CLSM using fluorescently labeled gel. The optimized formulation achieved high entrapment efficiency (~ 81.56%), small vesicle size (~ 360.15 nm), and stability, showing a larger inhibition zone than marketed cream, higher 24-hour cumulative drug release, minimal skin irritation, and confirmed deep skin penetration into the epidermis and dermis.