Activity of immunoglobulin G-coated red cell ghosts containing pentamidine against macrophage-contained Leishmania in vitro.
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 micrograms of encapsulated drug resulted in a calculated drug concentration of 180 micrograms/ml macrophage, and in 73% suppression of organism multiplication within the macrophages after 4-5 days of further cultivation. In comparison, 27 micrograms unencapsulated drug/ml was needed for similar suppression. Electron microscopic examination 5 hours after phagocytosis 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.
D000578:Amidines / Q000494:pharmacology*; D000818:Animals; D004910:Erythrocyte Membrane / Q000276:immunology* / Q000469:parasitology; D007074:Immunoglobulin G / Q000276:immunology*; D007891:Leishmania / Q000187:drug effects* / Q000276:immunology / Q000648:ultrastructure; D008264:Macrophages / Q000469:parasitology* / Q000648:ultrastructure; D051379:Mice; D008807:Mice, Inbred BALB C; D008854:Microscopy, Electron; D010419:Pentamidine / Q000008:administration & dosage / Q000494:pharmacology*; D010587:Phagocytosis; D012756:Sheep
D000578:Amidines; D007074:Immunoglobulin G; D010419:Pentamidine