Candicidal Effect of a Nanoemulsion Based on the Essential Oil of the Medicinal Plant Haplopappus foliosus: Role of Main Compounds in Yeast Inhibition

Background/Objectives: The increasing resistance of Candida species to conventional antifungals, particularly azoles, poses a critical public health challenge due to high mortality rates associated with candidemia. This study aimed to describe the chemical composition of the essential oil from Haplopappus foliosus (EO-BAI) and evaluate its antifungal properties, along with its nanoemulsion (NE-BAI) and major constituents, against a panel of clinical Candida isolates. Methods: EO-BAI was extracted via steam distillation and analyzed using GC-MS. A nanoemulsion was synthesized through ultrasonic emulsification and characterized by DLS and microscopy (SEM/STEM). Antifungal activity (MIC/MFC) was determined following CLSI M27-A3 guidelines. Time–kill kinetic studies were conducted on C. albicans, and an in silico approach was used to describe interactions with Als9-2 and CYP51 targets. Results: The EO-BAI profile was dominated by terpinen-4-ol (27.27%) and α-bisabolol (10.40%). The NE-BAI exhibited a droplet size of approximately 22 nm with an encapsulation efficiency of 88.72%. Among the tested samples, α-bisabolol emerged as the core bioactive driver (MIC = 16 µg/mL against C. albicans). While NE-BAI showed reduced initial activity at 24 h, it demonstrated enhanced efficacy by 48 h, matching fluconazole’s potency and maintaining a definitive fungicidal effect. Docking analysis confirmed that α-bisabolol establishes stabilizing interactions with key virulence and membrane homeostasis targets. Conclusions: The NE-BAI provides a sustained delivery of its bioactive terpenes, preserving their fungicidal nature and positioning them as robust therapeutic alternatives to conventional treatments.