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 investiga ted the action of free pentamidine, compared with pentamidine bound to polymethacrylate nanoparticles, in a rodent model. BALB/c mice were i nfected, via the tail vein, with 4 x 10(7) L. mater (MON 74) promastig otes. Twelve days after infection, seven groups of mice were treated r espectively with methylglucamine antimoniate (Glucatime(R)) 5.56 mg/kg i.p. x 5 d., pentamidine bound nanoparticles (100 mu M), unloaded pol ymethacrylate nanoparticles, unloaded nanoparticles associated with fr ee pentamidine (100 mu M) 0.1 ml i.v. x 3 d and free pentamidine iseth ionate (2.28 mg/kg and 0.17 mg/kg i.v. x 3 d.). Twenty-one days past i nfection, the mice were sacrificed and the Leishmania load in the live r 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-pentam idine was approx. 12.