## 4 Discussion
parapsilosis_ (Figures 4 and 6), zones of growth inhibition were observed for the positive controls (voriconazole and amphotericin B) and for polyvinylpyrrolidone-voriconazole samples. The occurrence of growth inhibition zones indicates that these materials have antifungal activity against _C. parapsilosis_, resulting in a lack of observable colony forming units in the regions surrounding the samples. This observation suggests that the antifungal activity of the respective samples is not limited to a surface interaction between the thin films and the fungal cells. The anti-biofilm activity of the coatings tested against _C. albicans_ biofilms are shown in Figure 5. The growth inhibition zones surrounding the samples were noted for the positive controls, the polyvinylpyrrolidone-voriconazole samples, the polyvinylpyrrolidone-quercetin dihydrate-voriconazole samples, and the polyvinylpyrrolidone-resveratrol-voriconazole samples (Figure 6). The analysis of the coating efficiency against _C. albicans_ versus _C. parapsilosis_ biofilms indicated a statistically significant higher activity of voriconazole, polyvinylpyrrolidone-voriconazole, polyvinylpyrrolidone-quercetin dihydrate-voriconazole, and polyvinylpyrrolidone-resveratrol-voriconazole samples against _C. albicans_ biofilms as compared with _C. parapsilosis_ (two-way ANOVA, Bonferroni post-test, _p_! 0.001). The coating containing voriconazole embedded in polyvinylpyrrolidone and polyvinylpyrrolidone-quercetin dihydrate-voriconazole proved to be significantly more active than free voriconazole against _C. albicans_ biofilms (_p_! 0.05 and _p_! 0.0001, respectively). The coatings containing both voriconazole and quercetin dehydrate exhibited higher activity against _C. albicans_ biofilms as compared with the coatings containing either voriconazole or quercetin dehydrate alone (_p_! 0.001). In the case of _C. parapsilosis_ biofilms, the coatings containing polyvinylpyrrolidone-voriconazole proved to be more active than free voriconazole (_p_! 0.001). Our results are in agreement with other scientific reports, which demonstrates the synergy between polyvinylpyrrolidone or quercetin and azoles. For example, it was shown that quercetin combined with fluconazole exhibited synergistic activity against the _C. albicans_ biofilm formed by strains isolated from patients with vulvovaginal candidiasis due to the inhibition of cell-cell adhesion and the expression of genes responsible for biofilm formation (e.g., _ALSI, HWPI, SUIN41, UME6, PBS2_, and _PDE2_) [29]. Polyvinylpyrrolidone polymer is used as a granulation binder excipient for voriconazole tablets [30]. Other recent studies demonstrated synergy between polyvinylpyrrolidone-coated silver nanoparticles (Ag-NPs) and azole antifungals (e.g., voriconazole) against a drug-resistant _C. albicans_ strain. Several changes were detected after the combination treatment, including disruption of cell membrane integrity, the tendency of polyvinylpyrrolidone-coated Ag-NPs to adhere to the cell membrane, inhibition of the budding process, as well as defects in ergosterol signaling and efflux pump functions [31]. The synergic antifungal activity of polyvinylpyrrolidone, quercetin, and voriconazole may be explained by better interaction of fluconazole with the fungal cells and/or biofilm matrix, the inhibition of intercellular communication and adhesion, changes in gene expression profile, alteration of membrane permeability, and interference with cellular wall synthesis. The lack of observable colony forming units in the zones surrounding these samples is indicative of an antifungal effect that is not limited to contact between the thin films and the organisms. However, although no zones of growth inhibition in the regions surrounding the samples were recorded in the case of the other tested samples, the fungal growth was completely inhibited in the area located below the tested specimen. The negative controls did not induce any fungal growth inhibition.