Facile Green Synthesis of Zinc Oxide Nanoparticles with Potential Synergistic Activity with Common Antifungal Agents against Multidrug-Resistant Candidal Strains

Abstract

The high incidence of fungal resistance to antifungal drugs represents a global concern, contributing to high levels of morbidity and mortality, especially among immunocompromised patients. Moreover, conventional antifungal medications have poor therapeutic outcomes, as well as possible toxicities resulting from long-term administration. Accordingly, the aim of the present study was to investigate the antifungal effectiveness of biogenic zinc oxide nanoparticles (ZnO NPs) against multidrug-resistant candidal strains. Biogenic ZnO NPs were characterized using physicochemical methods, such as UV-vis spectroscopy, transmission electron microscopy (TEM), energy-dispersive X ray (EDX) spectroscopy, FTIR (Fourier transform infrared) spectroscopy and X-ray powder diffraction (XRD) analysis. UV spectral analysis revealed the formation of two absorption peaks at 367 and 506 nm, which preliminarily indicated the successful synthesis of ZnO NPs, whereas TEM analysis showed that ZnO NPs exhibited an average particle size of 22.84 nm. The EDX spectrum confirmed the successful synthesis of ZnO nanoparticles free of impurities. The FTIR spectrum of the biosynthesized ZnO NPs showed different absorption peaks at 3427.99, 1707.86, 1621.50, 1424.16, 1325.22, 1224.67, 1178.22, 1067.69, 861.22, 752.97 and 574.11 cm−1, corresponding to various functional groups. The average zeta potential value of the ZnO NPs was −7.45 mV. XRD analysis revealed the presence of six diffraction peaks at 2θ = 31.94, 34.66, 36.42, 56.42, 69.54 and 76.94°. The biogenic ZnO NPs (100 µg/disk) exhibited potent antifungal activity against C. albicans, C. glabrata and C. tropicalis strains, with suppressive zone diameters of 24.18 ± 0.32, 20.17 ± 0.56 and 26.35 ± 0.16 mm, respectively. The minimal inhibitory concentration (MIC) of ZnO NPs against C. tropicalis strain was found to be 10 μg/mL, whereas the minimal fungicidal concentration (MFC) was found to be 20 μg/mL. Moreover, ZnO NPs revealed a potential synergistic efficiency with fluconazole, nystatin and clotrimazole antifungal drugs against C. albicans strain, whereas terbinafine, nystatin and itraconazole antifungal drugs showed a potential synergism with ZnO NPs against C. glabrata as a multidrug-resistant strain. In conclusion, pomegranate peel extract mediated green synthesis of ZnO NPs with potential physicochemical features and antimicrobial activity. The biosynthesized ZnO NPs could be utilized for formulation of novel drug combinations to boost the antifungal efficiency of commonly used antifungal agents.