title: Therapeutic evaluation of free and liposome-loaded furazolidone in experimental visceral leishmaniasis.
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 0.5mg/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 (50mg/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.
authors.affiliation: Laboratory of Applied Toxinology on Antiparasitic Drugs, Department of Parasitology, Instituto Adolfo Lutz, Av Dr Arnaldo 355, 8 degrees andar, CEP 01246-000 São Paulo, Brazil. atempone@ial.sp.gov.br
authors.forename: André Gustavo
authors.initials: AG
authors.lastname: Tempone
authors.forename: Renato Arruda
authors.initials: RA
authors.lastname: Mortara
authors.forename: Heitor Franco
authors.initials: HF
authors.lastname: de Andrade
authors.forename: Juliana Quero
authors.initials: JQ
authors.lastname: Reimão
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000008:administration & dosage*; D002478:Cells, Cultured; D006224:Cricetinae; D016503:Drug Delivery Systems; D004353:Drug Evaluation, Preclinical; D005260:Female; D005664:Furazolidone / Q000008:administration & dosage*; D007274:Injections, Intraperitoneal; D007891:Leishmania / Q000187:drug effects*; D007898:Leishmaniasis, Visceral / Q000188:drug therapy*; D008081:Liposomes; D017737:Macrophages, Peritoneal / Q000469:parasitology; D008297:Male; D008647:Mesocricetus; D051379:Mice; D008807:Mice, Inbred BALB C
chemical_list: D000981:Antiprotozoal Agents; D008081:Liposomes; D005664:Furazolidone