Anticandidal and Antibiofilm Activity of the Essential Oils from the Leaves of Citrus limon and Citrus sinensis

<i>Candida albicans</i> is an opportunistic pathogen whose virulence factors, such as polymorphism and biofilm formation, facilitate infection. Due to rising antifungal resistance, essential oils (EOs) from <i>Citrus limon</i> and <i>Citrus sinensis</i> are being investigated for their antimicrobial potential. This study analyzes the chemical composition, antifungal activity against <i>Candida albicans</i> in planktonic and biofilm forms, cytotoxicity on human erythrocytes, and pharmacokinetic properties of <i>Citrus limon</i> and <i>Citrus sinensis</i> essential oils. The essential oils were extracted from the leaves by hydrodistillation, and their composition was analyzed by GC-MS. Antifungal activity was assessed using broth microdilution and time-kill kinetics. Combined effects were assessed using checkerboard assays, while antibiofilm tests were evaluated using polystyrene plate assays and microscopy. Hemolytic activity tests were performed using percentage hemolysis. <i>C. limon</i> essential oil had limonene 40.8%, <i>β</i>-pinene 16.5%, and citronellal 12.3%, while <i>C. sinensis</i> had limonene 36.7%, <i>β</i>-pinene 14.6%, and eucalyptol 10.5% as its main constituents. The MIC was 0.312 - 1.25 mg/mL, with kill kinetics of up to 10 h. It showed additive effects for <i>C. limon</i>/fluconazole and synergistic effects for <i>C. sinensis</i>/fluconazole. It exhibited anti-adhesion and anti-polymorphism effects, inhibiting biofilm formation. It also exhibited low cytotoxicity, with an LC₅₀ of 14 000 µg/mL for <i>C. limon</i> and 13 000 µg/mL for <i>C. sinensis</i>. ADMET and BOILED-egg pharmacokinetic predictions indicated safety for systemic use, with caution for topical application of limonene, citronellal, and eucalyptol. Both EOs exhibited strong anti-<i>Candida</i> activity with minimal cytotoxicity. Its additive/synergistic effects with fluconazole highlight its potential as an alternative or adjuvant therapy against <i>C. albicans</i> infections.