Fabrication and Evaluation of Voriconazole Loaded Transethosomal Gel for Enhanced Antifungal and Antileishmanial Activity

Abstract

Voriconazole (VRC) is a broad-spectrum antifungal agent belonging to BCS class II (bio-pharmaceutical classification system). Despite many efforts to enhance its solubility, this primary issue still remains challenging for formulation scientists. Transethosomes (TELs) are one of the potential innovative nano-carriers for improving the solubility and permeation of poorly soluble and permeable drugs. We herein report voriconazole-loaded transethosomes (VRCT) fabricated by the cold method and followed by their incorporation into carbopol 940 as a gel. The prepared VRCT were evaluated for % yield, % entrapment efficiency (EE), surface morphology, possible chemical interaction, particle size, zeta potential, and polydispersity index (PDI). The optimized formulation had a particle size of 228.2 nm, a zeta potential of −26.5 mV, and a PDI of 0.45 with enhanced % EE. Rheology, spreadability, extrudability, in vitro release, skin permeation, molecular docking, antifungal, and antileishmanial activity were also assessed for VRCT and VRC loaded transethosomal gel (VTEG). Ex-vivo permeation using rat skin depicted a transdermal flux of 22.8 µg/cm2 /h with enhanced efficiency up to 4-fold. A two-fold reduction in inhibitory as well as fungicidal concentra-tion was observed against various fungal strains by VRCT and VTEG besides similar results against L-donovani. The development of transethosomal formulation can serve as an efficient drug delivery system through a topical route with enhanced efficacy and better patient compliance.