Formulation and antifungal performance of natamycin-loaded liposomal suspensions: the benefits of sterol-enrichment

Abstract

The aim of this study is to develop and evaluate food-grade liposomal delivery systems for the antifungal compound natamycin. Liposomes made of various soybean lecithins are prepared by solvent injection, leading to small unilamellar vesicles (<130 nm) with controlled polydispersity, able to encapsulate natamycin without significant modification of their size characteristics. Presence of charged phospholipids and reduced content of phosphatidylcholine in the lecithin mixture are found to be beneficial for natamycin encapsulation, indicating electrostatic interactions of the preservative with the polar head of the phospholipids. The chemical instability of natamycin upon storage in these formulations is however significant and proves that uncontrolled leakage out of the liposomes occurs. Efficient prevention of natamycin degradation is obtained by incorporation of sterols (cholesterol, ergosterol) in the lipid mixture and is linked to higher entrapment levels and reduced permeability of the phospholipid membrane provided by the ordering effect of sterols. Comparable action of ergosterol is observed at concentrations 2.5-fold lower than cholesterol and attributed to a preferential interaction of natamycin–ergosterol as well as a higher control of membrane permeability. Fine-tuning of sterol concentration allows preparation of liposomal suspensions presenting modulated in vitro release kinetics rates and enhanced antifungal activity against the model yeast Saccharomyces cerevisiae.

• Antifungal performance
• cholesterol
• ergosterol
• natamycin
• solvent injection

Acknowledgements

The authors would like to thank Paul H.H. Bomans (Soft Matter CryoTEM Research Unit, Eindhoven University of Technology) and Camille Carcouët (DSM Ahead) for performing the cryo-TEM analyses.

Declaration of interest

The authors would like to acknowledge financial support from the European Union (Marie Curie Actions 7th Framework, Initial Training Network PowTech, grant agreement no. 264722) and DSM Food Specialties.