Efficacy of Lychnopholide polymeric nanocapsules after oral and intravenous administration in murine experimental Chagas disease.
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2016
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Abstract
The etiological treatment of Chagas disease remains neglected. The compounds available show several limitations, mainly during
the chronic phase. Lychnopholide encapsulated in polymeric nanocapsules (LYC-NC) was efficacious in mice infected with
Trypanosoma cruzi and treated by intravenous administration during the acute phase (AP). As the oral route is preferred for
treatment of chronic infections, such as Chagas disease, this study evaluated the use of oral LYC-NC in the AP and also compared
it with LYC-NC administered to mice by the oral and intravenous routes during the chronic phase (CP). The therapeutic
efficacy was evaluated by fresh blood examination, hemoculture, PCR, and enzyme-linked immunosorbent assay (ELISA). The
cure rates in the AP and CP were 62.5% and 55.6%, respectively, upon oral administration of LYC–poly(D,L-lactide)–polyethylene
glycol nanocapsules (LYC-PLA-PEG-NC) and 57.0% and 30.0%, respectively, with LYC–poly- -caprolactone nanocapsules
(LYC-PCL-NC). These cure rates were significantly higher than that of free LYC, which did not cure any animals. LYC-NC formulations
administered orally during the AP showed cure rates similar to that of benznidazole, but only LYC-NC cured mice in
the CP. Similar results were achieved with intravenous treatment during the CP. The higher cure rates obtained with LYC loaded
in PLA-PEG-NC may be due to the smaller particle size of these NC and the presence of PEG, which influence tissue diffusion
and the controlled release of LYC. Furthermore, PLA-PEG-NC may improve the stability of the drug in the gastrointestinal tract.
This work is the first report of cure of experimental Chagas disease via oral administration during the CP. These findings represent
a new and important perspective for oral treatment of Chagas disease.
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MELLO, C. G. C. et al. Efficacy of Lychnopholide polymeric nanocapsules after oral and intravenous administration in murine experimental Chagas disease. Antimicrobial Agents and Chemotherapy, v. 60, p. 5215-5222, 2016. Disponível em: <http://aac.asm.org/content/60/9/5215.long>. Acesso em: 29 ago. 2017.