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

• Published in: International journal of pharmaceutics Vol. 662; p. 124486
• Main Authors: Augis, Luc, Nguyễn, Cảnh Hưng, Ciseran, Cécile, Wacha, András, Mercier-Nomé, Françoise, Domenichini, Séverine, Sizun, Christina, Fourmentin, Sophie, Legrand, François-Xavier
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 05.09.2024; Elsevier
• Subjects: Amphotericin B; Cutaneous leishmaniasis; Deep eutectic solvents; Franz diffusion cells; Galenic pharmacology; Life Sciences; Lipophilic solution; Low transition temperature mixtures; MTT assay; Pharmaceutical sciences; Cutaneous leishmaniasis; Amphotericin B; Deep eutectic solvents; Franz diffusion cells; Lipophilic solution; Low transition temperature mixtures; MTT assay
• ISSN: 0378-5173; 1873-3476; 1873-3476
• DOI: 10.1016/j.ijpharm.2024.124486

[Display omitted] 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.