Treatment of rabbits with atherosclerosis induced by cholesterol feeding with daunorubicin associated to a lipid core nanoparticle (LDE)

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art_ALBUQUERQUE_Treatment_of_rabbits_with_atherosclerosis_induced_by_cholesterol_2023.PDF (3.94 MB)
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0
Tipo de produção
article
Data de publicação
2023
DOI
Scopus
Web of Science
Título da Revista
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Título do Volume
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ELSEVIER
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Citação
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY, v.79, article ID 104067, 10p, 2023
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Atherosclerosis is a cell-proliferative, chronic inflammatory process. The aim was to investigate whether lipid core nanoparticles (LDE) carrying the anti-cancer agent daunorubicin could have anti-atherosclerotic effects. LDE is taken-up by cellular lipoprotein receptors and is capable of concentrating incorporated drugs in inflammed tissues. New Zealand male rabbits were fed 1% cholesterol diet for 8 weeks. Then, animals were treated with LDE-daunorubicin (6 mg/kg/week, IV, n = 9) or with LDE only (n = 7). Atherosclerotic lesions in LDE-daunorubicin group were 50% smaller than in LDE group. In LDE-daunorubicin, protein expressions of the pro-inflammatory markers CD68, TNF-alpha IL-6 and gene expression MCP-1 were lower than in LDE. Gene expression of IL-1 beta, IL-18 and IL-10 were similar. Protein expressions of VEGF and of pro-apoptotic caspase 3, caspase 9 and BAX, and both protein and gene expressions of VCAM-1 were all lower in LDE-daunorubicin. Gene expression of MMP-12 and protein expression of MMP-2 were lower in LDE-daunorubicin, but MMP-9 was not different. Daunorubicin is known as cardiotoxic, but at echocardiography, LDE-daunorubicin had no differences in arch aorta diameters, systolic and diastolic function and in cardiac hypertrophy compared to LDE group. LDEdaunorubicin was capable of reducing atherosclerotic lesions by different mechanisms without observable toxicities.
Palavras-chave
Drug toxicity, Drug delivery, Lipid nanoparticles, Inflammation, Cardiotoxicity, Chemotherapeutic agents
URI
https://observatorio.fm.usp.br/handle/OPI/51439
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Coleções
Artigos e Materiais de Revistas Científicas - FM/MCP
Artigos e Materiais de Revistas Científicas - HC/InCor
Artigos e Materiais de Revistas Científicas - LIM/11
Artigos e Materiais de Revistas Científicas - ODS/03