Cure of experimental Chagas' disease by the bis-triazole DO870 incorporated into 'stealth' polyethyleneglycol-polylactide nanospheres.
We have incorporated several inhibitors of sterol biosynthesis into long-circulating polyethyleneglycol-polylactide (PEG-PLA) nanospheres in order to improve the bioavailability of these poorly soluble compounds. Mice infected with CL and Y strains of Trypanosoma cruzi and treated for 30 consecutive days with DO870-loaded nanospheres at doses of 3 mg/kg/day, by the intravenous route, showed a significant cure rate (60-90%) for both strains. The activity was dose dependent and significant activity was observed for doses > or = 0.75 mg/kg/day. No cure was observed in mice treated with unloaded nanoparticles. Ketoconazole and itraconazole failed to induce cure against the Y strain even in the entrapped form.
Molina
J
J
Laboratório de Doença de Chagas, Centro de Pesquisas René Rachou, Belo Horizonte, Brazil.
Urbina
J
J
Gref
R
R
Brener
Z
Z
Rodrigues Júnior JM
D000818:Animals; D014355:Chagas Disease / Q000188:drug therapy* / Q000378:metabolism / Q000469:parasitology; D004195:Disease Models, Animal; D004337:Drug Carriers; D016503:Drug Delivery Systems; D005260:Female; D051379:Mice; D008863:Microspheres; D011091:Polyesters; D011092:Polyethylene Glycols; D016896:Treatment Outcome; D014230:Triazoles / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D014344:Trypanocidal Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D014349:Trypanosoma cruzi / Q000187:drug effects
D004337:Drug Carriers; D011091:Polyesters; D014230:Triazoles; D014344:Trypanocidal Agents; C058219:ICI 195739; D011092:Polyethylene Glycols; C033616:poly(lactide)