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 the activity of antileishmanial compounds. In view of such a strategy, we loaded the antileishmanial agent pentamidine on polymethacrylate nanoparticles. The activity of pentamidine-loaded nanoparticles was compared with that of free pentamidine in a BALB/c mice model of visceral leishmaniasis induced by Leishmania infantum. On day 0, mice were infected intravenously with 10(7) promastigotes and then treated via the tail vein on days 14, 16 and 18 with bound pentamidine, free drug or isotonic saline (control group). On day 21, liver parasite burdens were evaluated using the Stauber method. Livers and spleens were removed and weighed. Effective doses (ED) were determined using the Michaelis-Menten 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 value calculated for bound pentamidine was 1 mg kg-1. It was not possible to obtain the ED90 for free pentamidine because the dose-response curve reached a plateau near 60% of parasite suppression. A significant decrease in liver and spleen weights, probably reflecting the leishmanicidal 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.
Durand
R
R
Laboratoire de Parasitologie, Faculté de Médecine de Créteil, France. rjdurand@worldnet.fr
Paul
M
M
Rivollet
D
D
Houin
R
R
Astier
A
A
Deniau
M
M
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D004339:Drug Compounding; D018314:Leishmania infantum / Q000187:drug effects*; D007898:Leishmaniasis, Visceral / Q000188:drug therapy*; D008099:Liver / Q000469:parasitology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009929:Organ Size; D010419:Pentamidine / Q000627:therapeutic use*; D011109:Polymethacrylic Acids; D013154:Spleen / Q000469:parasitology; D014344:Trypanocidal Agents / Q000627:therapeutic use*
D004337:Drug Carriers; D011109:Polymethacrylic Acids; D014344:Trypanocidal Agents; C030613:polymethacrylic acid; D010419:Pentamidine