Cutaneous leishmaniasis, caused by Leishmania parasites, requires treatments with
fewer side effects than those currently available. The development of a topical solution
based on amphotericin B (AmB) was pursued. The considerable interest in deep eutectic
solvents (DESs) and their remarkable advantages inspired the search for a suitable
hydrophobic excipient. Various mixtures based on commonly used hydrogen bond donors
(HBDs) and acceptors (HBAs) for DES preparations were explored. Initial physical and
in-vitro screenings showed the potential of quaternary phosphonium salt-based mixtures.
Through thermal analysis, it was determined that most of these mixtures did not exhibit
eutectic behavior. X-ray scattering studies revealed a sponge-like nanoscale structure.
The most promising formulation, based on a combination of trihexyl(tetradecyl)phosphonium
chloride and 1-oleoyl-rac-glycerol, showed no deleterious effects through histological
evaluation. AmB was fully solubilized at concentrations between 0.5 and 0.8 mg·mL−1,
depending on the formulation. The monomeric state of AmB was observed by circular
dichroism. In-vitro irritation tests demonstrated acceptable viability for AmB-based
formulations up to 0.5 mg·mL−1. Additionally, an ex-vivo penetration study on pig
ear skin revealed no transcutaneous passage, confirming AmB retention in healthy,
unaffected skin.
