Development of a ZnO–chitosan nano-delivery platform encapsulating Matricaria chamomilla essential oil for multi-target inhibition of Candida albicans

The increasing prevalence of candidiasis caused by Candida albicans and the limited efficacy of conventional therapies necessitate the development of advanced antifungal drug delivery systems with improved bioavailability and multi-target activities from natural sources. Nanoencapsulation of plant essential oils (EOs) as safe and effective antifungals in drug delivery systems has shown to improve the EOs solubility, stability, and bioavailability. In this study, a ZnO–chitosan nanocomposite encapsulating Matricaria chamomilla essential oil (ZnO–CS–MCEO) was developed and further evaluated for antifungal activity against C. albicans . The nanocomposite was characterized by SEM, XRD, FTIR, and DLS analyses. Synthesized ZnO–CS–MCEO exhibited a mean particle size of 100 nm, a polydispersity index of 0.469, zeta potential of 25.9 mv and an encapsulation efficiency of 75%, indicating successful loading and colloidal stability. ZnO–CS–MCEO showed MIC and MFC values of 125 and 250 µg/mL against C. albicans in CLSI broth microdulution assay. The nanocomposite inhibited the fungal biofilm formation and ergosterol content of by 71.76% and 65.57% at MIC concentration, accordingly. Mechanistic investigations revealed time-dependent potassium leakage, significant induction of intracellular ROS, and severe ultrastructural damages confirmed by TEM imaging in nanocomposite-treated C. albicans . Cytotoxicity assessment on L-929 fibroblasts cells showed no toxicity at MIC levels, supporting the biocompatibility of the ZnO–CS–MCEO. These findings indicate that the ZnO–CS–MCEO nano-delivery platform exerts multi-targeted antifungal effects through membrane disruption, oxidative stress induction, and inhibition of biofilm-associated virulence factors, representing an efficient therapeutic tool for the management of candidiasis.