title: In vitro and in vivo trypanocidal activity of H2bdtc-loaded solid lipid nanoparticles.
abstract: The parasite Trypanosoma cruzi causes Chagas disease, which remains a serious public health concern and continues to victimize thousands of people, primarily in the poorest regions of Latin America. In the search for new therapeutic drugs against T. cruzi, here we have evaluated both the in vitro and the in vivo activity of 5-hydroxy-3-methyl-5-phenyl-pyrazoline-1-(S-benzyl dithiocarbazate) (H2bdtc) as a free compound or encapsulated into solid lipid nanoparticles (SLN); we compared the results with those achieved by using the currently employed drug, benznidazole. H2bdtc encapsulated into solid lipid nanoparticles (a) effectively reduced parasitemia in mice at concentrations 100 times lower than that normally employed for benznidazole (clinically applied at a concentration of 400 µmol kg(-1) day(-1)); (b) diminished inflammation and lesions of the liver and heart; and (c) resulted in 100% survival of mice infected with T. cruzi. Therefore, H2bdtc is a potent trypanocidal agent.
authors.affiliation: Faculdade de Ciências Farmacêuticas de Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Zumira A
authors.initials: ZA
authors.lastname: Carneiro
authors.affiliation: Instituto de Química de São Carlos, University of São Paulo, São Carlos, São Paulo, Brazil.
authors.forename: Pedro I da S
authors.initials: PI
authors.lastname: Maia
authors.affiliation: Departamento de Bioquímica e Imunologia, School of Medicine, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Renata
authors.initials: R
authors.lastname: Sesti-Costa
authors.affiliation: Departamento de Bioquímica e Imunologia, School of Medicine, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Carla D
authors.initials: CD
authors.lastname: Lopes
authors.affiliation: Faculdade de Ciências Farmacêuticas de Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Tatiana A
authors.initials: TA
authors.lastname: Pereira
authors.affiliation: Departamento de Bioquímica e Imunologia, School of Medicine, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Cristiane M
authors.initials: CM
authors.lastname: Milanezi
authors.affiliation: Instituto de Física de São Carlos, University of São Paulo, São Carlos, São Paulo, Brazil; Centro Universitário Central Paulista - UNICEP, São Carlos, São Paulo, Brazil.
authors.forename: Marcelo A Pereira
authors.initials: MA
authors.lastname: da Silva
authors.affiliation: Faculdade de Ciências Farmacêuticas de Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Renata F V
authors.initials: RF
authors.lastname: Lopez
authors.affiliation: Departamento de Bioquímica e Imunologia, School of Medicine, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: João S
authors.initials: JS
authors.lastname: Silva
authors.affiliation: Instituto de Química de São Carlos, University of São Paulo, São Carlos, São Paulo, Brazil.
authors.forename: Victor M
authors.initials: VM
authors.lastname: Deflon
mesh_terms: D000818:Animals; D014355:Chagas Disease; D004195:Disease Models, Animal; D005260:Female; D006321:Heart / Q000187:drug effects / Q000469:parasitology; D008055:Lipids / Q000008:administration & dosage*; D008099:Liver / Q000187:drug effects / Q000469:parasitology; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D018512:Parasitemia / Q000188:drug therapy; D013859:Thiocarbamates / Q000008:administration & dosage* / Q000737:chemistry; D014344:Trypanocidal Agents / Q000008:administration & dosage* / Q000737:chemistry; D014349:Trypanosoma cruzi / Q000187:drug effects
chemical_list: D008055:Lipids; D013859:Thiocarbamates; D014344:Trypanocidal Agents