Therapeutic evaluation of free and liposome-loaded furazolidone in experimental visceral leishmaniasis

Author(s)

Tempone, Andre Gustavo ^[1] ; Mortara, Renato Arruda ^[2] ; de Andrade, Jr., Heitor Franco ^[3] ; Reimao, Juliana Quero ^[1]

Affiliation

^[1] Inst Adolfo Lutz Registro, Dept Parasitol, Lab Appl Toxinol Antiparasit Drugs, BR-01246000 Sao Paulo - Brazil

^[2] Escola Paulista Med, UNIFESP, Dept Microbiol Imunol & Parasitol, BR-0403902 Sao Paulo - Brazil

^[3] Univ Sao Paulo, Lab Protozool, Inst Trop Med, BR-05603000 Sao Paulo - Brazil

• Document type: Journal article
• Source: INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS; v. 36, n. 2, p. 159-163, AUG 2010.
• Web of Science Citations: 19

Abstract

Drug delivery systems are promising pharmaceutical formulations used to improve the therapeutic index of drugs. In this study, we developed a liposomal formulation of furazolidone that targets Leishmania (Leishmania) chagasi amastigotes in a hamster model. Using laser scanning confocal microscopy, it was demonstrated that the liposomal drug co-localised with L. (L.) chagasi amastigotes within macrophages. Liposomal furazolidone administered intraperitoneally at 0.5 mg/kg for 12 consecutive days reduced spleen (74%) and liver (32%) parasite burden at a 100-fold lower dose than the free drug. Free furazolidone (50 mg/kg) also effectively reduced spleen (82.5%) and liver (85%) parasites; its in vitro activity against promastigotes and intracellular amastigotes demonstrated a high degree of parasite selectivity. Thus, furazolidone, both in the free and liposome-loaded formulation, is an effective inhibitor of L. (L.) chagasi, representing a possible cost-effective drug candidate for the treatment of visceral leishmaniasis. (C) 2010 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved. (AU)

• FAPESP's process: 08/09260-7 - Therapeutic combinations for visceral leishmaniasis: the antileishmanial potential of calcium channel blockers and the use of liposomal nanoformulations
• Grantee: André Gustavo Tempone Cardoso
• Support Opportunities: Regular Research Grants