Polyester nanocapsules for intravenous delivery of artemether : formulation development, antimalarial efficacy, and cardioprotective effects in vivo.

Registro completo de metadados
MetadadosDescriçãoIdioma
Autor(es): dc.creatorDiniz, Alessandra Teixeira Vidal-
Autor(es): dc.creatorGuimarães, Homero Nogueira-
Autor(es): dc.creatorGarcia, Giani Martins-
Autor(es): dc.creatorBraga, Érika Martins-
Autor(es): dc.creatorRichard, Sylvain-
Autor(es): dc.creatorGuimarães, Andrea Grabe-
Autor(es): dc.creatorMosqueira, Vanessa Carla Furtado-
Data de aceite: dc.date.accessioned2025-08-21T15:12:02Z-
Data de disponibilização: dc.date.available2025-08-21T15:12:02Z-
Data de envio: dc.date.issued2023-09-29-
Data de envio: dc.date.issued2023-09-29-
Data de envio: dc.date.issued2021-
Fonte completa do material: dc.identifierhttp://www.repositorio.ufop.br/jspui/handle/123456789/17515-
Fonte completa do material: dc.identifierhttps://doi.org/10.3390/polym14245503-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/capes/1005516-
Descrição: dc.descriptionArtemether (ATM) is an effective antimalarial drug that also has a short half-life in the blood. Furthermore, ATM is also cardiotoxic and is associated with pro-arrhythmogenic risks. We aimed to develop a delivery system enabling the prolonged release of ATM into the blood coupled with reduced cardiotoxicity. To achieve this, we prepared polymeric nanocapsules (NCs) from different biodegradable polyesters, namely poly(D,L-lactide) (PLA), poly-ε-caprolactone (PCL), and surface-modified NCs, using a monomethoxi-polyethylene glycol-block-poly(D,L-lactide) (PEG5kDa- PLA45kDa) polymer. Using this approach, we were able to encapsulate high yields of ATM (>85%, 0–4 mg/mL) within the oily core of the NCs. The PCL-NCs exhibited the highest percentage of ATM loading as well as a slow release rate. Atomic force microscopy showed nanometric and spherical particles with a narrow size dispersion. We used the PCL NCs loaded with ATM for biological evaluation following IV administration. As with free-ATM, the ATM-PCL-NCs formulation exhibited potent antimalarial efficacy using either the “Four-day test” protocol (ATM total at the end of the 4 daily doses: 40 and 80 mg/kg) in Swiss mice infected with P. berghei or a single low dose (20 mg/kg) of ATM in mice with higher parasitemia (15%). In healthy rats, IV administration of single doses of free-ATM (40 or 80 mg/kg) prolonged cardiac QT and QTc intervals and induced both bradycardia and hypotension. Repeated IV administration of free-ATM (four IV doses at 20 mg/kg every 12 h for 48 h) also prolonged the QT and QTc intervals but, paradoxically, induced tachycardia and hypertension. Remarkably, the incorporation of ATM in ATM-PCL-NCs reduced all adverse effects. In conclusion, the encapsulation of ATM in biodegradable polyester NCs reduces its cardiovascular toxicity without affecting its antimalarial efficacy.-
Formato: dc.formatapplication/pdf-
Idioma: dc.languageen-
Direitos: dc.rightsaberto-
Direitos: dc.rightsThis article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). Fonte: PDF do artigo.-
Palavras-chave: dc.subjectQT interval-
Palavras-chave: dc.subjectCardiotoxicity-
Palavras-chave: dc.subjectMalaria-
Palavras-chave: dc.subjectSelf-assembled polymers-
Palavras-chave: dc.subjectPolylactide-
Título: dc.titlePolyester nanocapsules for intravenous delivery of artemether : formulation development, antimalarial efficacy, and cardioprotective effects in vivo.-
Aparece nas coleções:Repositório Institucional - UFOP

Não existem arquivos associados a este item.