ACTIVITY OF PENTAMIDINE-LOADED METHACRYLATE NANOPARTICLES AGAINST LEISHMANIA-INFANTUM IN A MOUSE MODEL

The use of drug delivery systems may reduce the toxicity and improve t he activity of antileishmanial compounds. In view of such a strategy, we loaded the antileishmanial agent pentamidine on polymethacrylate na noparticles. The activity of pentamidine-loaded nanoparticles was comp ared with that of free pentamidine in a BALB/c mice model of visceral leishmaniasis induced by Leishmania infantum. On day 0, mice were infe cted intravenously with 10(7) promastigotes and then treated via the t ail vein on days 14, 16 and 18 with bound pentamidine, free drug or is otonic saline (control group). On day 21, liver parasite burdens were evaluated using the Stauber method. Livers and spleens were removed an d neighed. Effective doses (ED) were determined using the Michaelis-Me nten representation relating the percentage of parasite suppression to the dose. The ED50 of bound pentamidine was six times lower than that of free pentamidine (0.17 mg kg(-1) vs 1.06 mg kg(-1)). The ED90 valu e calculated for hound pentamidine was 1 mg kg(-1). It was not possibl e to obtain the ED90 for free pentamidine because the dose-response cu rve reached a plateau near 60% of parasite suppression. A significant decrease in liver and spleen weights, probably reflecting the leishman icidal activity, was observed for treated mice with bound pentamidine. These results showed that bound pentamidine was more potent than the free drug against L. infantum in our BALB/c mice model. (C) 1997 Austr alian Society for Parasitology. Published by Elsevier Science Ltd.