Hydrophobic binary mixtures containing amphotericin B as lipophilic solutions for the treatment of cutaneous leishmaniasis
- TR Number: 1054
- Authors: Luc Augis, Cảnh Hưng Nguyễn, Cécile Ciseran, András Wacha, Françoise Mercier-Nomé, Séverine Domenichini, Christina Sizun, Sophie Fourmentin, François-Xavier Legrand
- Materials Tested: 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
- Link to PDF: https://www.sciencedirect.com/science/article/pii/S0378517324007208
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.