Lychnopholide in Poly(D,L-Lactide)-block-polyethylene glycol nanocapsules cures infection with a drug-resistant Trypanosoma cruzi strain at acute and chronic phases.

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dc.contributor.authorBranquinho, Renata Tupinambá
dc.contributor.authorMello, Carlos Geraldo Campos de
dc.contributor.authorOliveira, Maykon Tavares de
dc.contributor.authorReis, Levi Eduardo Soares
dc.contributor.authorVieira, Paula Melo de Abreu
dc.contributor.authorGuimarães, Dênia Antunes Saúde
dc.contributor.authorMosqueira, Vanessa Carla Furtado
dc.contributor.authorLana, Marta de
dc.date.accessioned2021-11-23T14:15:57Z
dc.date.available2021-11-23T14:15:57Z
dc.date.issued2020pt_BR
dc.description.abstractChagas disease remains neglected, and current chemotherapeutics present severe limitations. Lychnopholide (LYC) at low doses loaded in polymeric poly(D,L-lactide)-block-polyethylene glycol (PLA-PEG) nanocapsules (LYC-PLA-PEG-NC) exhibits anti-Trypanosoma cruzi efficacy in mice infected with a partially drugresistant strain. This study reports the efficacy of LYC-PLA-PEG-NC at higher doses in mice infected with a T. cruzi strain resistant to benznidazole (BZ) and nifurtimox (NF) treated at both the acute phase (AP) and the chronic phase (CP) of infection by the oral route. Mice infected with the T. cruzi VL-10 strain were treated by the oral route with free LYC (12 mg/kg of body weight/day), LYC-PLA-PEG-NC (8 or 12 mg/kg/day), or BZ at 100 mg/kg/day or were not treated (controls). Treatment efficacy was assessed by hemoculture (HC), PCR, enzyme-linked immunosorbent assay (ELISA), heart tissue quantitative PCR (qPCR), and histopathology. According to classical cure criteria, treatment with LYC-PLA-PEG-NC at 12 mg/kg/day cured 75% (AP) and 88% (CP) of the animals, while at a dose of 8 mg/kg/day, 43% (AP) and 43% (CP) were cured, showing dose-dependent efficacy. The negative qPCR results for heart tissue and the absence of inflammation/fibrosis agreed with the negative results obtained by HC and PCR. Thus, the mice treated with the highest dose could be considered 100% cured, in spite of a low ELISA reactivity in some animals. No cure was observed in animals treated with free LYC or BZ or the controls. These results are exceptional in terms of experimental Chagas disease chemotherapy and provide evidence of the outstanding contribution of nanotechnology in mice infected with a T. cruzi strain totally resistant to BZ and NF at both phases of infection. Therefore, LYC-PLA-PEG-NC has great potential as a new treatment for Chagas disease and deserves further investigations in clinical trials.pt_BR
dc.identifier.citationBRANQUINHO, R. T. et al. Lychnopholide in Poly(D,L-Lactide)-block-polyethylene glycol nanocapsules cures infection with a drug-resistant Trypanosoma cruzi strain at acute and chronic phases. Antimicrobial Agents and Chemotherapy, v. 64, p. e01937-19, abr. 2020. Disponível em: <https://journals.asm.org/doi/10.1128/AAC.01937-19>. Acesso em: 10 jun. 2021.pt_BR
dc.identifier.doihttps://doi.org/10.1128/AAC.01937-19pt_BR
dc.identifier.issn1098-6596
dc.identifier.urihttp://www.repositorio.ufop.br/jspui/handle/123456789/14008
dc.identifier.uri2https://journals.asm.org/doi/10.1128/AAC.01937-19pt_BR
dc.language.isoen_USpt_BR
dc.rightsrestritopt_BR
dc.subjectOral treatmentpt_BR
dc.titleLychnopholide in Poly(D,L-Lactide)-block-polyethylene glycol nanocapsules cures infection with a drug-resistant Trypanosoma cruzi strain at acute and chronic phases.pt_BR
dc.typeArtigo publicado em periodicopt_BR
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