Action of pentamidine-bound nanoparticles against Leishmania on an in vivo model.
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 10(7) 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 microM), unloaded polymethacrylate nanoparticles, unloaded nanoparticles associated with free pentamidine (100 microM) 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.
Fusai
T
T
Laboratoire de Parasitologie, Faculté de Médecine, Créteil.
Deniau
M
M
Durand
R
R
Bories
C
C
Paul
M
M
Rivollet
D
D
Astier
A
A
Houin
R
R
D000818:Animals; D000965:Antimony / Q000494:pharmacology / Q000627:therapeutic use; D000981:Antiprotozoal Agents / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D003102:Colloids; D004195:Disease Models, Animal; D004337:Drug Carriers; D005260:Female; D018320:Leishmania major / Q000187:drug effects*; D007898:Leishmaniasis, Visceral / Q000188:drug therapy*; D008099:Liver / Q000469:parasitology; D008536:Meglumine / Q000494:pharmacology / Q000627:therapeutic use; D000077485:Meglumine Antimoniate; D051379:Mice; D008807:Mice, Inbred BALB C; D008863:Microspheres; D009942:Organometallic Compounds / Q000494:pharmacology / Q000627:therapeutic use; D010419:Pentamidine / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D011109:Polymethacrylic Acids; D011897:Random Allocation
D000981:Antiprotozoal Agents; D003102:Colloids; D004337:Drug Carriers; D009942:Organometallic Compounds; D011109:Polymethacrylic Acids; C030613:polymethacrylic acid; D010419:Pentamidine; D008536:Meglumine; D000077485:Meglumine Antimoniate; D000965:Antimony