Antileishmanial activity of liposome-encapsulated meglumine antimonate in the dog.

Experimental infections of Leishmania donovani in mixed-breed dogs were induced to determine the antileishmanial efficacy of liposome-encapsulated meglumine antimoniate ( LEMA ). Each dog was inoculated IV with 1.0 +/- 0.2 X 10(8) amastigotes of a Khartoum strain of L donovani/kg of body weight. The antileishmanial agents ( LEMA or unencapsulated meglumine antimoniate ) were given once daily, IV, for 1, 4, or 10 consecutive days beginning the 12th day after inoculation. The dogs were killed 3 or 4 days after completion of therapy, and parasites in the spleens were quantified. A single injection of LEMA (0.61 mg of Sb/kg of body weight) resulted in 89% suppression and 4 consecutive daily injections of LEMA (1.94 mg of Sb/kg/day) resulted in 95.8% suppression of splenic parasites. The dose of LEMA that would give 50% suppression ( SD50 ) was estimated as approximately 0.029 mg of Sb/kg. The SD50 for unencapsulated drug was estimated as approximately 24 mg of Sb/kg. The liposome-encapsulated drug was estimated to be more than 700 times more efficacious than the unencapsulated drug. Seemingly, liposomes can markedly reduce the drug dosage required for equivalent treatment of visceral leishmaniasis in dogs.