Lychnopholide in Poly(d,l-Lactide)- Block -Polyethylene Glycol Nanocapsules Cures Infection with a Drug-Resistant Trypanosoma cruzi Strain at Acute and Chronic Phases.

Autor:	Branquinho RT; Programa de Pós-Graduação em Ciências Farmacêuticas, Escola de Farmácia, Universidade Federal de Ouro Preto, Minas Gerais, Brazil.; Programa de Pós-Graduação em Ciências Biológicas, Núcleo de Pesquisa em Ciências Biológicas (NUPEB), Universidade Federal de Ouro Preto, Minas Gerais, Brazil., de Mello CGC; Programa de Pós-Graduação em Ciências Farmacêuticas, Escola de Farmácia, Universidade Federal de Ouro Preto, Minas Gerais, Brazil., Oliveira MT; Programa de Pós-Graduação em Ciências Biológicas, Núcleo de Pesquisa em Ciências Biológicas (NUPEB), Universidade Federal de Ouro Preto, Minas Gerais, Brazil., Reis LES; Programa de Pós-Graduação em Ciências Biológicas, Núcleo de Pesquisa em Ciências Biológicas (NUPEB), Universidade Federal de Ouro Preto, Minas Gerais, Brazil., Vieira PMA; Programa de Pós-Graduação em Ciências Biológicas, Núcleo de Pesquisa em Ciências Biológicas (NUPEB), Universidade Federal de Ouro Preto, Minas Gerais, Brazil., Saúde-Guimarães DA; Programa de Pós-Graduação em Ciências Farmacêuticas, Escola de Farmácia, Universidade Federal de Ouro Preto, Minas Gerais, Brazil., Mosqueira VCF; Programa de Pós-Graduação em Ciências Farmacêuticas, Escola de Farmácia, Universidade Federal de Ouro Preto, Minas Gerais, Brazil.; Programa de Pós-Graduação em Ciências Biológicas, Núcleo de Pesquisa em Ciências Biológicas (NUPEB), Universidade Federal de Ouro Preto, Minas Gerais, Brazil., de Lana M; Programa de Pós-Graduação em Ciências Farmacêuticas, Escola de Farmácia, Universidade Federal de Ouro Preto, Minas Gerais, Brazil delana@nupeb.ufop.br.; Programa de Pós-Graduação em Ciências Biológicas, Núcleo de Pesquisa em Ciências Biológicas (NUPEB), Universidade Federal de Ouro Preto, Minas Gerais, Brazil.
Jazyk:	angličtina
Zdroj:	Antimicrobial agents and chemotherapy [Antimicrob Agents Chemother] 2020 Mar 24; Vol. 64 (4). Date of Electronic Publication: 2020 Mar 24 (Print Publication: 2020).
DOI:	10.1128/AAC.01937-19
Abstrakt:	Chagas 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 drug-resistant 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. (Copyright © 2020 American Society for Microbiology.)
Databáze:	MEDLINE
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