ACTIVITY OF PENTAMIDINE-LOADED POLY-(D,L-LACTIDE) NANOPARTICLES AGAINST LEISHMANIA-INFANTUM IN A MURINE MODEL

The activity of pentamidine-loaded poly(D,L-lactide) nanoparticles was compared, by determination of median effective doses (ED50) to that o f free pentamidine in a murine model of visceral leishmaniasis induced by Leishmania infantum. BALB/c mice were infected intravenously on da y 0 with promastigotes and then treated on days 14, 16, and 18. Groups of 5 mice received either 0.57, 1.14 and 2.28 mg/kg of free pentamidi ne (expressed in pentamidine base) or 0.055, 0.11, 0.22 and 0.44 mg/kg of pentamidine-loaded nanoparticles. In the control group, 12 mice re ceived normal saline. The liver parasite burden was evaluated using th e Stauber method 72 h after the last injection and drug levels in live rs and spleens were determined. Bound pentamidine was 3.3 times more a ctive than free drug (ED50 value = 0.32 mg/kg versus 1.05 mg/kg for fr ee drug]. Drug levels showed a weak accumulation in hepatic and spleni c tissues following bound pentamidine administration. A lock of acute toxicity was noted in all groups treated by bound pentamidine. Results obtained with this biodegradable carrier may be of particular interes t as no new major antileishmanial compound is today available.