Cure of experimental Chagas' disease by the bis-triazole DO870 incorporated into 'stealth' polyethyleneglycol-polylactide nanospheres

J Antimicrob Chemother. 2001 Jan;47(1):101-4. doi: 10.1093/jac/47.1.101.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chagas Disease / drug therapy*
  • Chagas Disease / metabolism
  • Chagas Disease / parasitology
  • Disease Models, Animal
  • Drug Carriers
  • Drug Delivery Systems
  • Female
  • Mice
  • Microspheres
  • Polyesters
  • Polyethylene Glycols
  • Treatment Outcome
  • Triazoles / administration & dosage
  • Triazoles / pharmacokinetics
  • Triazoles / therapeutic use*
  • Trypanocidal Agents / administration & dosage
  • Trypanocidal Agents / pharmacokinetics
  • Trypanocidal Agents / therapeutic use*
  • Trypanosoma cruzi / drug effects

Substances

  • Drug Carriers
  • Polyesters
  • Triazoles
  • Trypanocidal Agents
  • ICI 195739
  • Polyethylene Glycols
  • poly(lactide)