Hexadecylphosphocholine: oral treatment of visceral leishmaniasis in mice

TLDR

Hexadecylphosphocholine (He‑PC), a novel phospholipid derivative, was evaluated in vitro against Leishmania donovani and Leishmania infantum. He‑PC showed potent in vitro activity (IC50 0.89–2.25 µg ml⁻¹) and, when given orally to infected BALB/c mice, produced marked antileishmanial effects, achieving liver parasite suppression comparable to subcutaneous sodium stibogluconate after 5 days but superior reductions in spleen and bone marrow, with a >600‑fold greater spleen parasite clearance after 4 weeks.

Abstract

Hexadecylphosphocholine (He-PC), a novel phospholipid derivative, was tested against Leishmania donovani and Leishmania infantum, the causative agents of visceral leishmaniasis. In vitro, promastigotes were highly susceptible to He-PC; the 50% inhibitory concentrations were between 0.89 and 2.25 micrograms/ml for the different leishmanial strains. In vivo, a marked antileishmanial activity in infected BALB/c mice could be demonstrated after oral administration of He-PC. Whereas parasite suppression and killing in the liver were comparable after 5 days of treatment with He-PC (10 or 20 mg/kg of body weight per day administered orally) and sodium stibogluconate (120 mg of pentavalent antimonal agent per kg/day administered subcutaneously), a superior reduction in the parasite load in the spleen and bone marrow was observed after oral treatment with He-PC. After a 4-week treatment period, parasite suppression in the spleen was better than that observed with standard sodium stibogluconate therapy by a factor of more than 600.