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 Syzygium aromaticum (formerly Eugenia caryophyllata ) (clove) and Cymbopogon flexuosus (lemongrass) on Candida albicans (individually, and in combination) and incorporate them into hydrogels for the management of oral candidiasis. Method The antifungal activity of both essential oils singly and in combination was performed using macro and checkerboard dilution against a standard C. albicans (ATCC 10231) and 14 clinical isolates. 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.