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Título: | Polyester nanocapsules for intravenous delivery of artemether : formulation development, antimalarial efficacy, and cardioprotective effects in vivo. |
Autor(es): | Diniz, Alessandra Teixeira Vidal Guimarães, Homero Nogueira Garcia, Giani Martins Braga, Érika Martins Richard, Sylvain Guimarães, Andrea Grabe Mosqueira, Vanessa Carla Furtado |
Palavras-chave: | QT interval Cardiotoxicity Malaria Self-assembled polymers Polylactide |
Data do documento: | 2022 |
Referência: | DINIZ, A. T. V. et al. Polyester nanocapsules for intravenous delivery of artemether : formulation development, antimalarial efficacy, and cardioprotective effects in vivo. Polymers, v. 14, n. 24, artigo 5503, 2022. Disponível em: <https://www.mdpi.com/2073-4360/14/24/5503>. Acesso em: 01 ago. 2023. |
Resumo: | Artemether (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. |
URI: | http://www.repositorio.ufop.br/jspui/handle/123456789/17515 |
DOI: | https://doi.org/10.3390/polym14245503 |
ISSN: | 073-4360 |
Licença: | This 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. |
Aparece nas coleções: | DEFAR - Artigos publicados em periódicos |
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Arquivo | Descrição | Tamanho | Formato | |
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ARTIGO_PolyesterNanocapsulesIntravenous.pdf | 2,13 MB | Adobe PDF | Visualizar/Abrir |
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