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Activity of Immunoglobulin G-Coated Red Cell Ghosts Containing Pentamidine Against Macrophage-Contained Leishmania In Vitro
J. D. Berman
J. D. Berman
Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Department of Pediatrics, U.S.U.H.S., Washington, D.C. 20307
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M. Aikawa
M. Aikawa
Institute of Pathology, Case Western Reserve University, Cleveland, Ohio 44106
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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 µg of encapsulated drug resulted in a calculated drug concentration of 180 µg/ml macrophage, and in 73% suppression of organism multiplication within the macrophages after 4–5 days of further cultivation. In comparison, 27 µg unencapsulated 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.
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