Hydrophobic binary mixtures containing amphotericin B as lipophilic solutions for the treatment of cutaneous leishmaniasis

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 AmBbased 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.

EpiDerm EPI-200-SIT, EpiDermFT EFT-400,  skin irritation, OECD 439, immunostaining, Ki67, filaggrin, transglutaminase-1, TGM-1, Aquaporin-3, E-Cadherin, Claudin-1, Occludin, Cytokeratin-1, CK1, CK10,  TUNEL, epidermal thickness, cell junction tightness. water balance, skin elasticity, apoptosis, tetrabutylphosphonium chloride, tetraoctylammonium chloride, methyltrioctylammonium chloride, tetrabutylammonium chloride, tetrabutylphosphonium, octanoic acid, decanoic acid, dodecanoic acid, tetradecanoic acid, hexadecanoic acid, octadecanoic acid, tetradecan-1-ol, octadecan-1-ol, sodium dodecyl sulfate, Decan-1-ol, hexadecan-1-ol, trihexyl (tetradecyl) phosphonium chloride, trihexyl(octyl)phosphonium chloride, dodecan-1-ol, 1-Oleoyl-rac-glycerol, monoolein

tetrabutylphosphonium chloride, tetraoctylammonium chloride, methyltrioctylammonium chloride, tetrabutylammonium chloride, tetrabutylphosphonium, octanoic acid, decanoic acid, dodecanoic acid, tetradecanoic acid, hexadecanoic acid, octadecanoic acid, tetradecan-1-ol, octadecan-1-ol, sodium dodecyl sulfate, Decan-1-ol, hexadecan-1-ol, trihexyl (tetradecyl) phosphonium chloride, trihexyl(octyl)phosphonium chloride, dodecan-1-ol, 1-Oleoyl-rac-glycerol, monoolein