Tioconazole (TCZ) is a broad-spectrum fungicidal BCS class II drug with reported activity against Candida albicans, dermatophytes, and certain Staphylococci bacteria. We report the use of TCZ-loaded transethosomes (TEs) to overcome the skin’s barrier function. TCZ-loaded TEs were fabricated by using a cold method with slight modification. Box–Behnken composite design was utilized to investigate the effect of independent variables. The fabricated TEs were assessed with various physicochemical characterizations. The optimized formulation of TCZ-loaded TEs was incorporated into gel and evaluated for pH, conductivity, drug content, spreadability, rheology, in vitro permeation, ex vivo permeation, and in vitro and in vivo antifungal activity. The fabricated TCZ-loaded TEs had a % EE of 60.56 to 86.13, with particle sizes ranging from 219.1 to 757.1 nm. The SEM images showed spherically shaped vesicles. The % drug permeation was between 77.01 and 92.03. The kinetic analysis of all release profiles followed Higuchi’s diffusion model. The FTIR, DSC, and XRD analysis showed no significant chemical interactions between the drug and excipients. A significantly higher antifungal activity was observed for TCZ-loaded transethosomal gel in comparison to the control. The in vivo antifungal study on albino rats indicated that TCZ-loaded transethosomal gel showed a comparable therapeutic effect in comparison to the market brand Canesten^®. Molecular docking demonstrated that the TCZ in the TE composition was surrounded by hydrophobic excipients with increased overall hydrophobicity and better permeation. Therefore, TCZ in the form of transethosomal gel can serve as an effective drug delivery system, having the ability to penetrate the skin and overcome the stratum corneum barrier with improved efficacy.

Hydroxypropyl β-cyclodextrin (HPβCD) based polymeric nanobeads containing voriconazole (VRC) were fabricated by free radical polymerization using N, N′-methylene bisacrylamide (MBA) as a cross-linker, 2-acrylamide-2-methylpropane sulfonic acid (AMPS) as monomer and ammonium persulfate (APS) as reaction promoter. Optimized formulation (CDN5) had a particle size of 320 nm with a zeta potential of −35.5 mV and 87% EE. Scanning electron microscopy (SEM) depicted porous and non-spherical shaped beads. No evidence of chemical interaction was evident in FT-IR studies, whereas distinctive high-intensity VRC peaks were found superimposed in XRD. A stable polymeric network formation was evident in DSC studies owing to a lower breakdown in VRC loaded HPβCD in comparison to blank HPβCD. In vitro release studies showed 91 and 92% drug release for optimized formulation at pH 1.2 and 6.8, respectively, with first-order kinetics as the best-fit model and non-Fickian diffusion as the release mechanism. No evidence of toxicity was observed upon oral administration of HPβCD loaded VRC polymeric nanobeads owing to with cellular morphology of vital organs as observed in histopathology. Molecular docking indicates the amalgamation of the compounds highlighting the hydrophobic patching mediated by nanogel formulation. It can be concluded that the development of polymeric nanobeads can be a promising tool to enhance the solubility and efficacy of hydrophobic drugs such as VRC besides decreased toxicity and for effective management of fungal infections.