Antifungal Efficacy of Plasma-Activated Liquids against Candida albicans: A Potential Alternative for Oral Candidiasis Treatment

Abstract

The increasing incidence of oral candidiasis refractory to conventional antifungal treatments, coupled with limited therapeutic alternatives, underscores an urgent need for novel interventions. Plasma-activated liquids (PALs), generated via nonthermal plasma, have shown antimicrobial promise, yet their antifungal efficacy, particularly against <i>Candida albicans</i>, remains understudied, and no investigations have addressed their use in oral candidiasis. In this study, PALs were produced using a gliding-arc plasma reactor with argon and compressed air (pure and mixed) at gas flows of 1.5 and 3.0 L/min, and an average power range of 25-60 W. Two liquid substrates, distilled water and 0.9% sodium chloride (saline) solution, were plasma-activated and characterized in terms of physicochemical parameters (pH, ORP, TDS, conductivity) and reactive oxygen and nitrogen species (RONS), including H₂O₂, NO₂ ^-, NO₃ ^-, HNO₂, and O₃, via spectrophotometry and reactive-strip analysis. The antifungal activity of PALs was assessed against <i>C. albicans</i> in both planktonic and biofilm forms. After 30 min exposure, argon-activated saline (S1) and distilled water (D1), and argon-air activated distilled water (D2), achieved ∼50% reduction in planktonic viability; only S1 and D1 maintained significant effects on 24- and 48 h biofilms. Moreover, PALs frozen at -18 °C for 24 h retained antifungal efficacy. Cytotoxicity assays using Vero cells confirmed that D1 and S1 were nontoxic over both immediate and 24 h exposures (viability &gt;70%). In sum, argon-derived PALs based on distilled water and saline exhibited selective antifungal and antibiofilm activity against <i>C. albicans</i>, without toxicity to mammal cells, highlighting their potential as adjunctive therapies in candidiasis management. These findings support further optimization for clinical applications.