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Antifungal Activity and Stability of Fluconazole Emulsion Containing Ionic Liquids Explained by Intermolecular
Bruno L Hennemann1, Caroline R Bender2, Guilherme S Moleta1
1Department of Chemistry, Federal University of Santa Maria, Santa Maria 97105900, Brazil.
Pharmaceutics
|April 23, 2022
Summary
Ionic liquids enhance fluconazole emulsion stability and antifungal activity, particularly [C16MIM]Br, showing improved efficacy against resistant Candida glabrata strains with low irritation potential.
Area of Science:
- Pharmaceutical Sciences
- Materials Science
- Biochemistry
Background:
- Fluconazole (FLZ) is a key antifungal agent, but its efficacy can be limited by formulation stability and resistance.
- Ionic liquids (ILs) offer tunable properties for drug delivery systems.
- Understanding intermolecular interactions is crucial for optimizing emulsion-based drug formulations.
Purpose of the Study:
- To evaluate the stability and antifungal activity of fluconazole emulsions prepared with specific ionic liquids ([CnMIM]Br).
- To investigate the intermolecular interactions between ionic liquids, medium-chain triglycerides (MCT), and fluconazole.
- To compare the antifungal efficacy of these novel emulsions against fluconazole alone and resistant fungal strains.
Main Methods:
- Accelerated stability experiments at 25 and 37 °C.
- Proton Nuclear Magnetic Resonance (1H NMR) spectroscopy to study interactions.
- Diffusion measurements to assess aggregate formation.
- Antifungal assays against Candida species, including resistant strains.
- HET-CAM assay for irritancy assessment.
Main Results:
- [C16MIM]Br based emulsions exhibited superior stability compared to [C12MIM]Br and those prepared by magnetic stirring (MS).
- Distinct interaction mechanisms were observed between ILs and MCT, and between ILs and fluconazole, with [C16MIM]Br forming more compact aggregates.
- Emulsions containing ILs demonstrated enhanced antifungal activity versus fluconazole alone, including potent inhibition of fluconazole-resistant Candida glabrata.
- All tested emulsions showed minimal irritant potential.
Conclusions:
- Ionic liquids, especially [C16MIM]Br, significantly improve the stability and antifungal potency of fluconazole emulsions.
- The observed interactions and aggregate formation influence emulsion performance.
- These IL-based fluconazole emulsions represent a promising strategy for treating fungal infections, including those caused by resistant strains.
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