Antifungal Cationic Nanoemulsion Ferrying Miconazole Nitrate with Synergism to Control Fungal Infections: In Vitro, Ex Vivo, and In Vivo Evaluations

[Image: see text] This study aimed to deliver a cationic nanoemulsion carrying miconazole nitrate (MCN) to control fungal infections using excipients for synergism. Peceol (oil) and labrasol (surfactant) were selected based on maximum solubility and zone of inhibition values against Candida albicans and Aspergillus niger. Optimized MCNE11 was evaluated [size, zeta potential, % entrapment efficiency (%EE), % transmittance, viscosity, refractive index, extrudability, polydispersity (PDI), morphology, and pH]. An in vitro drug release study was conducted for comparison between DS (drug suspension) and MNE11. In vitro hemolysis was studied at two different concentrations (0.625 and 2.5 μg/mL). Permeation profiles were generated using rat skin. A Draize test was conducted using rabbit to negate irritability issues. Finally, a stability test of MCNE11 was conducted for 12 months. The results showed that MCNE11 (cationic) was the most optimized in term of size, %EE, and PDI. The drug release from MCNE11 was higher compared to DS but comparable to MNE11 (anionic), suggesting no impact of the imposed cationic charge on the release behavior. Moreover, permeation parameters of MCNE11 were significantly (p < 0.05) greater than MNE11, which may be attributed to the combined impact of size (low), surfactant (for reversible changes), and electrostatic interaction (nanoglobules–skin surface). Thus, stable MCN11 possessing high %EE (89.8%), low size (145 nm), maximum flux (5.7 ± 0.1 μg/cm(2)/h), high drug deposition (932.7 ± 41.6 μg/cm(2)), optimal viscosity (44.17 ± 0.8 cP), low PDI (0.21), optimal zeta potential (+28.1 mV), and low hemolysis can be promising alternatives to conventional cream to control resistant and recurring types of fungal infections.