4300 | wileyonlinelibrary.com/journal/jam J Appl Microbiol. 2022;132:4300–4309. © 2022 Society for Applied Microbiology. Received: 13 January 2022 | Revised: 11 March 2022 | Accepted: 21 March 2022 DOI: 10.1111/jam.15542 ORIGINAL ARTICLE Activity of poly(methacrylic acid)-silver nanoparticles on fluconazole-resistant Candida albicans strains: Synergistic and cytotoxic effects Cecília Maria Cruz Falcão 1 | Audrey Andrade 2,3 | Vanderlan Nogueira Holanda 4 | Regina Celia Bressan Queiroz de Figueiredo 4 | Eulália Azevedo Ximenes 5 | Anderson Stevens Leonidas Gomes 1,2 1 Postgraduate Program in Dentistry, Federal University of Pernambuco, Recife, Brazil 2 Department of Physics, Federal University of Pernambuco, Recife, Brazil 3 Laboratory of Microscope and Microanalysis, Strategic Technologies Center of Northeast, Recife, Brazil 4 Department of Microbiology, Aggeu Magalhaes Research Centre, Recife, Brazil 5 Department of Antibiotics, Federal University of Pernambuco, Recife, Brazil Correspondence Cecília Maria Cruz Falcão, Postgraduate Program in Dentistry, Federal University of Pernambuco, 50670-901, Recife, Prince Edward Island, Brazil. Email: ceciliaodonto@gmail.com Funding information Conselho Nacional de Desenvolvimento Científico e Tecnológico, Grant/Award Number: PQ-1A 307259/2015-3; Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Grant/Award Number: 001CAPES-UFPE; Instituto Nacional de Fotônica, Grant/Award Number: INCT 465763/2014-6 Abstract Aims: To synthesize and evaluate the antifungal activity of poly(methacrylic acid)- silver nanoparticles (PMAA-AgNPs) against nine Candida albicans isolated from clinical specimens. Methods and Results: 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 cy- totoxicity 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 vi- ability for cells tested, with 50% cytotoxic concentration (CC 50 ) values of 6.5, 4.9 and 6.8 μg ml −1 for macrophages, fibroblasts and Vero cells, respectively. Conclusions: This study demonstrated that, in general, PMAA-AgNPs acts synergis- tically 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. Significance and Impact of Study: This study shows the potential of PMAA-AgNPs combined with fluconazole to inhibit fluconazole-resistant C. albicans strains. KEYWORDS Candida albicans, fluconazole, germ tube, silver nanoparticles, synergism Downloaded from https://academic.oup.com/jambio/article/132/6/4300/6988642 by guest on 20 January 2023