Activity of Immunoglobulin G-Coated Red Cell Ghosts Containing Pentamidine against Macrophage-Contained Leishmania in Vitro

摘要

Pentamidine is an antileishmanial agent that is often toxic at therapeutic dosages. The obligate intramacrophage localization of Leishmania indicates that encapsulation of pentamidine within a carrier phagocytized by macrophages (IgG-coated sheep red cell ghosts) might improve activity. In in vitro experiments, treatment of infected mouse macrophages for 1 hour with a mean of 1.4 ug of encapsulated drug resulted in a calculated drug concentration of 180 ug/ml macrophage, and in 73% suppression of organism multiplication within the macrophages after 4-5 days of further cultivation. In comparison, 27 ug encapsulated drug/ml was needed for similar suppression. Electron microscopic examination 5 hours after phagocystosis of IgG-ghosts revealed that 95% of organisms were adjacent to ghosts in phagolysosomes. Fusion of drug carrier with phagolysosome containing drug target is therefore an important step in carrier-mediated parasite suppression in this model. These results suggest that IgG-coated erythrocyte ghosts containing pentamidine have potential as an antileishmanial formation. (Author).