Platform for antifungal development in a nanostructured lipid system aiming at efficacy and safety in alternative animal models

Abstract

More than a billion people worldwide are estimated to suffer from some fungal disease and 1.5 to 2 million people die each year from a fungal infection, surpassing deaths from malaria or tuberculosis. Among these are those caused by Cryptococcus sp., Paracoccidioides sp. and Histoplasma capsulatum that are associated with high rates of morbidity and mortality. Treatment of these mycoses is by the combination of amphotericin B and azoles, with high toxicity and resistance rates. Although major advances have been made in the past decade, drug development has hardly evolved. Thus, the urgency to obtain new antifungal drugs stimulates the search for antimicrobial peptides. Additionally, the incorporation of these in nanostructured lipid systems becomes an important tool in the sense of controlled release, as well as the use of alternative animal models such as, Caenorhabditis elegans, Galleria mellonella and zebrafish (Danio rerio). In this work, linear and short peptides from wasps and scorpions will be tested for in vitro antifungal activity and cytotoxicity. The peptide with the best response in these tests will be selected to be associated with a nanostructured lipid system. The formulation will be characterized and tested in vivo, in which C. elegans, G. mellonella and zebrafish will be infected and the efficacy and toxicity will be assessed by observing the survival and fungal load of the animals.