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Activity of Immunoglobulin G-Coated Red Cell Ghosts Containing Pentamidine Against Macrophage-Contained Leishmania In Vitro^*

J. D. Berman AND M. Aikawa

Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Washington, D.C. 20307 and Department of Pediatrics, U.S.U.H.S., Bethesda, Maryland
Institute of Pathology, Case Western Reserve University, Cleveland, Ohio 44106

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.

Accepted for publication May 15, 1984.

^* This work was supported in part by research grants from the U.S. Army Research and Development Command (DAMD 17-79C-9209) and the U.S.P.H.S. (#AI 15351) to M.A.