28 research outputs found

    Activity of pentamidine-loaded poly (D, L-lactide) nanoparticles against

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    The activity of pentamidine-loaded poly(D, L-lactide) nanoparticles was compared, by determination of median effective doses (ED50), to that of free pentamidine in a murine model of visceral leishmaniasis induced by Leishmania infantum. BALB/с mice were infected intravenously on day 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 pentamidine (expressed in pentamidine base) or 0.055, 0.11, 0.22 and 0.44 mg/kg of pentamidine-loaded nanoparticles. In the control group, 1 2 mice received normal saline. The liver parasite burden was evaluated using the Stauber method 72 h after the last injection and drug levels in livers and spleens were determined. Bound pentamidine was 3.3 times more active than free drug (ED50 value = 0.32 mg/kg versus 1.05 mg/kg for free drug). Drug levels showed a weak accumulation in hepatic and splenic tissues following bound pentamidine administration. A lack of acute toxicity was noted in all groups treated by bound pentamidine. Results obtained with this biodegradable carrier may be of particular interest as no new major antileishmanial compound is today available

    Action of pentamidine-bound nanoparticles against

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    The efficiency of antileishmanial agents may be enhanced by improving their bioavailability with a colloidal drug carrier. We have investigated the action of free pentamidine, compared with pentamidine bound to polymethacrylate nanoparticles, in a rodent model. BALB/c mice were infected , via the tail vein , with 4 x 107 L. major (MON 74) promastigotes. Twelve days after infection, seven groups of mice were treated respectively with methylglucamine antimoniate (Glucantime®) 5.56 mg/kg i.p. x 5 d., pentamidine bound nanoparticles (100 μM), unloaded polymethacrylate nanoparticles, unloaded nanoparticles associated with free pentamidine (100 µM) 0.1 ml i.v. x 3 d and free pentamidine isethionate (2.28 mg/kg and 0.17 mg/kg i.v. x 3 d.). Twenty-one days post infection, the mice were sacrificed and the Leishmania load in the liver calculated from the number of amastigotes/500 liver cells and total liver weight in treated and untreated mice. Results demonstrated a 77 % amastigote reduction in the group treated with targeted pentamidine relative to the control group. The ratio free pentamidine/bound-pentamidine was approx. 12
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