An alternative approach for Malassezia-associated skin diseases treatments, a lysine-based emulsion

Abstract

The development of new therapeutic alternatives is gaining relevance in clinical treatments of different infectious diseases due to increased resistant strains with various resistance mechanisms. For Malassezia, resistance development against traditional antifungal drugs, such as azoles and amphotericin B, has been associated with mechanisms such as gene duplication and overexpression of antifungal targets and efflux pumps. In previous studies from our group, it was determined by in silico deletion of enzymes from a metabolic network reconstruction and in vitro inhibition assays that L-lysine could inhibit M. furfur, M. sympodialis, and M. pachydermatis growth. So, we consider the formulation of a lysine-based emulsion as a possible alternative for Malassezia-associated skin diseases. This study aims to formulate, prepare, and characterize an L-lysine emulsion capable of inhibiting Malassezia growth. The physical characterization of the emulsions consists of evaluating and determining their stability, rheologic properties, and drop size distribution. Meanwhile, the biological characterization describes its cytotoxicity against HEKa cells and in vivo models and its capacity to inhibit Malassezia growth in vitro. The creams have appropriate physical properties as it is stable in time, behave as pseudoplastic fluids, and have a PSD suitable for topical creams. The cream with the highest lysine concentration inhibited Malassezia in vitro at 10 and 5mg/mL. In contrast, at lower concentrations, could be observed an aberrant growth, meanwhile showing a mild cytotoxic effect which diminished when lysine concentration increased both in vitro and in vivo. The creams are stable, have a pseudoplastic behavior, and an adequate PSD as well as having an inhibitory effect on Malassezia's growth and mild cytotoxicity effect on HEKa cells and on Galleria mellonella model.