Simple, stable, non-toxic nanoemulsion of fluconazole containing imidazolium-based ionic liquids with acetate and amino acid-based anions.

In this work, imidazolium-based ionic liquids (ILs) bearing a 12-carbon alkyl chain (C12MIM) and carboxylate anions (acetate and phenylalaninate) were assessed as surfactants in the formulation of fluconazole-loaded nanoemulsions. Emulsification methodologies using ultrasound, ultra-turrax, and a combination of both were employed. Results showed that ILs with carboxylate anions are effective surfactants for producing stable fluconazole-loaded emulsions. Ultrasound was the most efficient emulsification method, yielding nano-sized, spherical droplets with low polydispersity and high stability. All emulsions had high encapsulation efficiency and cumulative drug release above 84 %. Strong antifungal activity was observed, particularly against Candida species, while cytotoxicity levels remained acceptable at biologically active concentrations. Hemolysis and HET-CAM tests confirmed good biocompatibility and low irritation potential, suggesting suitability for both topical and systemic applications.