In vitro and in vivo trypanocidal activity of H2bdtc-loaded solid lipid nanoparticles

Zumira A Carneiro; Pedro I da S Maia; Renata Sesti-Costa; Carla D Lopes; Tatiana A Pereira; Cristiane M Milanezi; Marcelo A Pereira da Silva; Renata F V Lopez; João S Silva; Victor M Deflon

doi:10.1371/journal.pntd.0002847

In vitro and in vivo trypanocidal activity of H2bdtc-loaded solid lipid nanoparticles

PLoS Negl Trop Dis. 2014 May 8;8(5):e2847. doi: 10.1371/journal.pntd.0002847. eCollection 2014 May.

Affiliations

¹ Faculdade de Ciências Farmacêuticas de Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
² Instituto de Química de São Carlos, University of São Paulo, São Carlos, São Paulo, Brazil.
³ Departamento de Bioquímica e Imunologia, School of Medicine, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
⁴ 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.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Chagas Disease
Disease Models, Animal
Female
Heart / drug effects
Heart / parasitology
Lipids / administration & dosage*
Liver / drug effects
Liver / parasitology
Mice
Nanoparticles / administration & dosage*
Nanoparticles / chemistry
Parasitemia / drug therapy
Thiocarbamates / administration & dosage*
Thiocarbamates / chemistry
Trypanocidal Agents / administration & dosage*
Trypanocidal Agents / chemistry
Trypanosoma cruzi / drug effects

Substances

Lipids
Thiocarbamates
Trypanocidal Agents

Grants and funding

This work was supported by the Research Foundation of the State of São Paulo” (FAPESP 2010/20610-0). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.