Efficacy of Lychnopholide Polymeric Nanocapsules after Oral and Intravenous Administration in Murine Experimental Chagas Disease.
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-ε-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.
Programa de Pós-Graduação em Ciências Farmacêuticas, Escola de Farmácia, Universidade Federal de Ouro Preto, Minas Gerais, Brazil.
Carlos Geraldo Campos
CG
de Mello
Programa de Pós-Graduação em Ciências Farmacêuticas, Escola de Farmácia, Universidade Federal de Ouro Preto, Minas Gerais, Brazil Núcleo de Pesquisa em Ciências Biológicas (NUPEB), Universidade Federal de Ouro Preto, Minas Gerais, Brazil.
Renata Tupinambá
RT
Branquinho
Núcleo de Pesquisa em Ciências Biológicas (NUPEB), Universidade Federal de Ouro Preto, Minas Gerais, Brazil.
Maykon Tavares
MT
Oliveira
Programa de Pós-Graduação em Ciências Farmacêuticas, Escola de Farmácia, Universidade Federal de Ouro Preto, Minas Gerais, Brazil.
Matheus Marques
MM
Milagre
Programa de Pós-Graduação em Ciências Farmacêuticas, Escola de Farmácia, Universidade Federal de Ouro Preto, Minas Gerais, Brazil Departamento de Farmácia, Escola de Farmácia, Universidade Federal de Ouro Preto, Minas Gerais, Brazil.
Dênia Antunes
DA
Saúde-Guimarães
Programa de Pós-Graduação em Ciências Farmacêuticas, Escola de Farmácia, Universidade Federal de Ouro Preto, Minas Gerais, Brazil Departamento de Farmácia, Escola de Farmácia, Universidade Federal de Ouro Preto, Minas Gerais, Brazil.
Vanessa Carla Furtado
VC
Mosqueira
Programa de Pós-Graduação em Ciências Farmacêuticas, Escola de Farmácia, Universidade Federal de Ouro Preto, Minas Gerais, Brazil Núcleo de Pesquisa em Ciências Biológicas (NUPEB), Universidade Federal de Ouro Preto, Minas Gerais, Brazil Departamento de Análises Clínicas, Escola de Farmácia, Universidade Federal de Ouro Preto, Minas Gerais, Brazil delana@nupeb.ufop.br.
Marta de
Md
Lana
D000208:Acute Disease; D061605:Administration, Intravenous; D000284:Administration, Oral; D000818:Animals; D014355:Chagas Disease / Q000188:drug therapy* / Q000401:mortality / Q000469:parasitology / Q000473:pathology; D002908:Chronic Disease; D003692:Delayed-Action Preparations / Q000737:chemistry / Q000494:pharmacology*; D004195:Disease Models, Animal; D004339:Drug Compounding / Q000379:methods; D006801:Humans; D007783:Lactones / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D053769:Nanocapsules / Q000008:administration & dosage / Q000737:chemistry*; D009593:Nitroimidazoles / Q000494:pharmacology; D011092:Polyethylene Glycols / Q000737:chemistry; D012717:Sesquiterpenes / Q000737:chemistry / Q000494:pharmacology*; D016019:Survival Analysis; D016896:Treatment Outcome; D014344:Trypanocidal Agents / Q000737:chemistry / Q000494:pharmacology*; D014349:Trypanosoma cruzi / Q000187:drug effects* / Q000254:growth & development / Q000472:pathogenicity
D003692:Delayed-Action Preparations; D007783:Lactones; D053769:Nanocapsules; D009593:Nitroimidazoles; D012717:Sesquiterpenes; D014344:Trypanocidal Agents; C427603:lychnopholide; C542623:monomethoxypolyethyleneglycol-polylactide block copolymer; D011092:Polyethylene Glycols; C009999:benzonidazole