In vitro activity of amphotericin B cochleates against Leishmania chagasi

Cochleate delivery vehicles are a novel lipid-based system with potential for delivery of amphotericin B (AmB). In this study, the efficacy of cochleates was evaluated by examining the in vitro activity of AmB cochleates (CAMB) against Leishmania chagasi in a macrophage model of infection. We demonstrate that CAMB is nontoxic to mac-rophages at concentrations as high as 2.5 µg/mL, whereas the conventional formulation, AmB deoxycholate, showed high toxicity at this concentration. The in vitro activity of CAMB against L. chagasi was found to be similar to that of the reference drug AmB deoxycholate, with ED50s of 0.017 µg/mL and 0.021 µg/mL, respectively. Considering that L. chagasi affects organs amenable to cochleate-mediated delivery of AmB, we hypothesize that CAMB will be an effective lipid system for the treatment of visceral leishmaniasis. Key words: amphotericin B cochleates- Leishmania chagasi- in vitro activity Despite its potent activity against leishmaniasis, the toxicity of the conventional formulation of amphotericin B (AmB) complexed with deoxycholate micelles limits its use in the treatment of visceral leishmaniasis (VL). To improve the therapeutic index of AmB and reduce its toxicity, new lipid-based formulations have been devel