Essential Oil and Supercritical Carbon Dioxide Extract of Grapefruit Peels Formulated for Candida albicans Infections: Evaluation by an in Vitro Model to Study Fungal–Host Interactions

[Image: see text] Resistance to currently available antifungal agents raises the need to develop alternative remedies. Candida albicans is the most common opportunistic pathogenic fungus of humans, colonizing in the genital and intestinal mucosa, skin, and oral-nasal cavity and reducing quality of life. Herein, essential oil from grapefruit (Citrus paradise) peels was obtained by hydrodistillation, and the remaining plant material was sequentially subjected to supercritical carbon dioxide (SC-CO(2)) extraction to determine the conditions for maximizing phenolic compounds. A statistical design was used to evaluate the effect of temperature (30, 50, 70 °C), pressure (80, 150, 220 bar), and ethanol as a cosolvent (0%, 10%, and 20% v/v). Essential oil and SC-CO(2) extracts were mixed at various ratios to develop an effective antifungal formulation. Subsequently, fungal infection was modeled by coculturing C. albicans with human skin keratinocytes (HaCaT) to mimic dermal mycoses, endothelial cells (HUVEC) to evaluate vascular fate, and cervical adenocarcinoma (HeLa) cells to represent additional genital mycoses. Treatment with essential oil and extract (25:75%) formulation for 8 h exhibited slight cytotoxicity toward HeLa cells, no toxicity toward HaCaT and HUVECs, whereas inhibition of C. albicans. Considering the clinical significance, such in vitro models are essential to screen potential compounds for the treatment of opportunistic fungal infections.