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Journal of Antimicrobial Chemotherapy (2001) 47, 101-104
© 2001 The British Society for Antimicrobial Chemotherapy

Brief report

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

Judith Molinaa,b, Julio Urbinac, Ruxandra Grefd, Zigman Brenera and José Maciel Rodrigues Júniore,*

a Laboratório de Doença de Chagas, Centro de Pesquisas René Rachou, Belo Horizonte, Brazil; b Departamento de Parasitología, Instituto de Zoología Tropical, Universidad Central de Venezuela, Caracas 1041, Venezuela; c Laboratorio de Química Biológica, Centro de Biofísica y Bioquímica, Instituto Venezolano de Investigaciones Científicas, Apartado 21827, Caracas 1020 A, Venezuela; d UMR CNRS 8612, Faculté de Pharmacie Chatenay-Malabry, France; e Laboratório de Tecnologia Farmacêutica, Departamento de Produtos Farmacêuticos, Universidade Federal de Minas Gerais, Brazil

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 >= 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.

* Correspondence address. Faculdade de Farmácia, Universidade Federal de Minas Gerais, Av. Olegário Maciel, 2360 CEP: 30180-112, Belo Horizonte (MG), Brazil. Fax: +55-31-291-97-69; E-mail: rodrigue{at}dedalus.lcc.ufmg.br


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