Key result
DO870-loaded nanospheres cure up to ~90% of Trypanosoma cruzi-infected mice vs unloaded nanoparticles.
Does not support clinical use in Chagas; leaves open further preclinical optimization of DO870 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.
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Judith Molina (2001) studied Chagas' disease. DO870-loaded PEG-PLA nanospheres vs. unloaded nanoparticles was evaluated on cure rate. Intravenous DO870-loaded PEG-PLA nanospheres at 3 mg/kg/day achieved a 60-90% cure rate in mice infected with Trypanosoma cruzi, compared to no cure with unloaded nanoparticles.
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