The differential effect of liposomal amphotericin B on human erythrocytes and promastigotes of Leishmania sp / Efecto diferencial de la anfotericina B ligada a liposomas sobre eritrocitos humanos y promastigotes de Leishmania sp

RESUMO

In this work, it was studied the effect that amphotericin B bound to liposomes (L-AmB) exerted on the potassium permeability of human erythrocytes and also on the rate of growth on culture of promastigotes of Leishmania sp. Liposomal amphotericin B was prepared by adding AmB to sonicated liposomes composed of egg-phosphatidylcholine (PC) or dipalmitoyl-phosphatidylcholine (DPPC). Incubation of human erythrocytes with free AmB (dissolved in organic solvent) led to a rapid enhancement of potassium efflux from erythrocytes. This permeabilizing effect of amphotericin B in erythrocytes decreased when the polyene antibiotic was added dissolved in a salt solution but it was negligible when AmB was added bound to liposomes (L-AmB). Liposomal AmB preparations made of PC or DPPC were equally effective in reducing AmB -induced potassium efflux from red cells to a minimum. By contrast, it was found that exposure of Leishmania promastigotes to liposomal AmB (PC or DPPC L-AmB) led to an inhibition of cell growth rate in a magnitude comparable to that exerted by AmB added in salt solution. Short term measurements of the magnitude of cell lysis after treating Leishmania promastigotes with amphotericin B revealed that the lytic effect of AmB added in aqueous solution, organic solvent or as PC-Liposomal AmB can be detected much earlier than that exerted by DPPC-Liposomal AmB. These results are discussed in terms of the differential capacity of AmB binding to liposomes of different composition and also on the characteristics of the mechanism of incorporation of AmB molecules to the membrane of target cells