Structural characterization of mixed micelles and gels of Soluplus-miltefosine-pentamidine for the treatment of cutaneous leishmaniasis

Leishmaniasis is a neglected tropical disease with high morbidity and mortality, considered the second leading cause of death worldwide by a parasitic agent after malaria. The available drugs against leishmaniasis exhibit high toxicity and long duration schedules, which can be overcome with more efficient formulations. Soluplus® (SLP), an amphiphilic graft copolymer made of polyethylene glycol and polyvinyl caprolactam-polyvinyl acetate, has gained significant attention in recent years due to its broad range of pharmaceutical applications. We propose to investigate through SANS the structure of mixed micelles and gels of SLP loaded with miltefosine (MF), an alkylphospholipid drug with antiparasitic activity, and pentamidine (PTM), both used for the treatment of this parasitic disease, as well as the phase behaviour of the systems under physiological conditions (buffered pH and controlled ionic strength). The experiments will cover the diluted regime (polymeric micelles) and the concentrated one, to address the formulation of MF/PTM-loaded gels for topical applications. The experiments proposed will be conducted in parallel with ongoing research based on different NMR methods, DLS and fluorescence spectroscopy, and with the evaluation of the toxicity and leishmanicidal activity (on macrophages, promastigotes and intracellular amastigotes) of the formulations.