Synergistic antifungal activity of lepidium sativum ZnO nanoparticles and nystatin against resistant candida species.

The rising threat of drug-resistant fungal pathogens such as Candida albicans poses a particular risk to disability patients, who often face heightened vulnerability to infections due to compromised immune function and frequent medical interventions, demanding innovative therapeutic approaches. This study presents a green synthesis of zinc oxide nanoparticles (ZnO-NPs) using Lepidium sativum seed extract as a promising strategy. The resulting ZnO-NPs were Characterized as crystalline with a hexagonal wurtzite structure and an average size of 32 nm. They demonstrated significant multifunctional biological activities, exhibiting potent, dose-dependent antifungal activity against Candida albicans and Candida tropicalis, with minimum inhibitory concentrations (MICs) of 125 µg/mL and 62.5 µg/mL, respectively. A key finding was the strong synergistic effect observed when ZnO-NPs were combined with nystatin, which showed an increase in fold area (IFA) of 0.85 and 0.99 against C. albicans and C. tropicalis, respectively. This synergistic interaction was further quantitatively confirmed by fractional inhibitory concentration index (FICI) values of 0.38 and 0.25 for the respective species. Furthermore, the ZnO-NPs displayed considerable antioxidant capacity (IC₅₀: 335.48 µg/mL) and promising selective cytotoxicity, demonstrating significantly greater potency against hepatoma (HUH7) cells (IC₅₀: 145.2 µg/mL) than against normal lung fibroblasts (WI38) (IC₅₀: 237.6 µg/mL). These results underscore the potential of L. sativum-derived ZnO-NPs as effective antifungal agents, particularly as adjuvants to enhance the efficacy of existing drugs like nystatin, while also offering antioxidant activity and favorable biocompatibility. This study advocates for further investigation into their mechanisms of action and in vivo efficacy to advance clinical applications.