Distribution of liposome-encapsulated antimony in dogs

Distribution of liposome-encapsulated antimony in dogs
February 2003
D.A. Schettini1, A.P. Costa Val3, L.F. Souza2, C. Demicheli4, O.G.F. Rocha5, M.N. Melo2, M.S.M. Michalick2 and F. Fr?zard1
Departamentos de 1Fisiologia e Biof?sica,
2Parasitologia, Instituto de Ci?ncias Biol?gicas,
3Departamento de Cl?nica e Cirurgia Veterin?rias, Escola Veterin?ria, and
4Departamento de Qu?mica, Instituto de Ci?ncias Exatas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brasil
5Laborat?rio de An?lise de Tra?os Met?licos, CETEC, Belo Horizonte, MG, Brasil
Brazilian Journal of Medical and Biological Research Volume 36(2) 269-272
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Abstract
The achievement of complete cure in dogs with visceral leishmaniasis is currently a great challenge, since dogs are the main reservoir for the transmission of visceral leishmaniasis to humans and they respond poorly to conventional treatment with pentavalent antimonials. In order to improve the efficacy of treatment, we developed a novel formulation for meglumine antimoniate based on the encapsulation of this drug in freeze-dried liposomes (LMA). The aim of the present study was to evaluate the biodistribution of antimony (Sb) in dogs following a single intravenous bolus injection of LMA. Four healthy male mongrel dogs received LMA at 3.8 mg Sb/kg body weight and were sacrificed 3, 48 and 96 h and 7 days later. Antimony was determined in the blood, liver, spleen and bone marrow. In the bone marrow, the highest Sb concentration was observed at 3 h (2.8 ?g/g wet weight) whereas in the liver and spleen it was demonstrated at 48 h (43.6 and 102.4 ?g/g, respectively). In these organs, Sb concentrations decreased gradually and reached levels of 19.1 ?g/g (liver), 28.1 ?g/g (spleen) and 0.2 ?g/g (bone marrow) after 7 days. Our data suggest that the critical organ for the treatment with LMA could be the bone marrow, since it has low Sb levels and, presumably, high rates of Sb elimination. A multiple dose treatment with LMA seems to be necessary for complete elimination of parasites from bone marrow in dogs with visceral leishmaniasis.
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