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.