3-Carene-loaded poloxamer micelles against Leishmania: Development, characterization and in vitro proof-of-concept

Leishmaniases are parasitic diseases that affect millions of people around the world. Pharmacotherapy has limitations emphasizing the urgency for cheaper, safer, and more effective treatment options. The anti-fungal 3carene (3CR) is a bicyclic monoterpene widely used by the perfume industry that has shown activity against some species of Leishmania. Despite its potential as a leishmanicidal compound, the high hydrophobicity of 3CR limits its therapeutic uses. Poloxamers are copolymers capable of self-organizing into micelles that have been widely used to deliver drugs in aqueous media, resulting in improved bioavailability. In this study, a series of micellar systems of poloxamer P407 isolated or combined with P188, P123, or L81 were developed to carry 3CR and enhance its activity against Leishmania braziliensis. The micellar systems showed hydrodynamic diameters and polydispersity indices that varied widely, influenced by the type and concentration of poloxamers. In the in vitro antipromastigote evaluation, the most expressive results were obtained with the association of P407/L81, where a reduction of three times or more was observed in the IC50 value, corroborating the potential added value of the developed self-assembled micelles containing the antifungal 3CR as a safe and low-cost therapeutic alternative for the treatment of leishmaniasis.