Biochemical insights into synergistic Candida biofilm disintegrating ability of p-cymene inclusion complex and miconazole

Abstract

Phytoactive molecules emerge as a plentiful reservoir of adjuvant and antifungal agents. The resolution of solubility and stability issues has been facilitated by developing molecular complexes or inclusion complexes of phytoactive molecules. Miconazole (MCZ) is a favoured azole with low off-target impact, however, its pharmacological efficacy requires a revamp to enhance its suitability as an antifungal drug. Hence, the present investigation delves into the mechanism of action of the p-cymene/β-cyclodextrin inclusion complex (IC) along with MCZ against Candida albicans and Candida glabrata biofilms. The synergy between IC and MCZ has been estimated at a concentration of 6.25 μg/mL IC + 0.5 μg/mL MCZ with a FICI of 0.19. The prepared IC + MCZ displayed remarkable antifungal properties against planktonic and sessile growth of Candida species. IC + MCZ exhibited a notable 80% biofilm eradication potential against both species, corroborated by morphological analysis using FE-SEM. The results indicated that IC/IC + MCZ acts by disrupting the biochemical composition of the ECM, altering the surface properties of the cells, reducing ergosterol, enhancing membrane permeability, and inducing oxidative stress. In conclusion, the study highlighted the synergistic antibiofilm activity of p-cymene IC with miconazole against Candida species. In summary, IC + MCZ has been established as a potent antifouling agent against Candida species, warranting further exploration for potential formulation with additional investigations.