Essential oil-based hydrogels for oral candidiasis: preliminary formulation development, antifungal efficacy, and computational analysis via Monte Carlo simulation.

Introduction: This study aimed to evaluate the inhibitory activity of the essential oils (EOs) of Method: The antifungal activity of both essential oils singly and in combination was performed using macro and checkerboard dilution against a standard Results and Discussion: Both EOs exhibited MIC of 100 μL/mL and MFC of 100 to 200 μL/mL depending on isolate; and a ΣFIC value of 0.75 indicating an additive outcome among 71% of the isolates. The EOs were formulated in hydrogels, the efficacies of which were tested using agar well diffusion method. The prepared hydrogels containing 3% w/w EOs in the ratio of 2:1 exhibited the best antifungal activity with desirably physicochemical and stability properties. Monte Carlo simulations (n = 10,000) further quantified the antifungal efficacy, revealing significantly enhanced inhibition arising from a synergistic effect of both EOs in combination. These findings highlight the promise of natural compounds as antifungal agents targeting critical fungal biosynthetic pathways and provide a basis for formulating EOs in hydrogels, potentially for the management of oral candidiasis.