Activity of poly(methacrylic acid)-silver nanoparticles on fluconazole-resistant Candida albicans strains: Synergistic and cytotoxic effects.

Abstract

To synthesize and evaluate the antifungal activity of poly(methacrylic acid)-silver nanoparticles (PMAA-AgNPs) against nine Candida albicans isolated from clinical specimens. The effects of PMAA-AgNPs-fluconazole combination was analysed by checkerboard methodology. The synergistic potential of PMAA-AgNPs-fluconazole was determined by the fractional inhibitory concentration index (FICI). The inhibition of germ tube formation and the determination of PMAA-AgNPs cytotoxicity were also performed. All C. albicans strains were susceptible to PMAA-AgNPs and resistant to fluconazole. PMAA-AgNPs at subinhibitory concentrations restored the susceptibility of resistant C. albicans to fluconazole, whose FICI ranged from 0.3 to 0.5. The synergistic interaction of the combination was observed in eight of nine strains. The PMAA-AgNPs-fluconazole combination was also able to inhibit the germ tube formation. PMAA-AgNPs showed a dose-dependent decrease in viability for cells tested, with 50% cytotoxic concentration (CC50 ) values of 6.5, 4.9 and 6.8μg ml-1 for macrophages, fibroblasts and Vero cells, respectively. This study demonstrated that, in general, PMAA-AgNPs acts synergistically in combination with fluconazole, inhibiting fluconazole-resistant C. albicans strains. PMAA-AgNPs-fluconazole combination was also able to inhibit germ tube formation, an important virulence factor. Inhibitory effect of PMAA-AgNPs alone or in combination was higher in C. albicans than in mammalian cells. This study shows the potential of PMAA-AgNPs combined with fluconazole to inhibit fluconazole-resistant C. albicans strains.