Doxorubicin-loaded pH-sensitive micelles: A promising alternative to enhance antitumor activity and reduce toxicity

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art_CAVALCANTE_Doxorubicinloaded_pHsensitive_micelles_A_promising_alternative_to_enhance_2021.PDF (6.24 MB)
Citações na Scopus
21
Tipo de produção
article
Data de publicação
2021
DOI
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Editora
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
Autores
CAVALCANTE, Carolina Henriques
FERNANDES, Renata Salgado
SILVA, Juliana de Oliveira
ODA, Caroline Mari Ramos
LEITE, Elaine Amaral
CASSALI, Geovanni Dantas
CHARLIE-SILVA, Ives
FERREIRA, Lucas Antonio Miranda
BARROS, Andre Luis Branco de
Citação
BIOMEDICINE & PHARMACOTHERAPY, v.134, article ID 111076, 11p, 2021
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Doxorubicin (DOX) is an anthracycline antibiotic widely used in the treatment of cancer, however, it is associated with the occurrence of adverse reactions that limits its clinical use. In this context, the encapsulation of DOX in micelles responsive to pH variations has shown to be a strategy for tumor delivery of the drug, with the potential to increase therapeutic efficacy and to reduce the toxic effects. In addition, radiolabeling nanoparticles with a radioactive isotope is of great use in preclinical studies, since it allows the in vivo monitoring of the nanostructure through the acquisition of quantitative images. Therefore, this study aimed to develop, characterize, and evaluate the antitumor activity of a pH-sensitive micelle composed of DSPE-PEG2000, oleic acid, and DOX. The micelles had a diameter of 13 nm, zeta potential near to neutrality, and high encapsulation percentage. The critical micellar concentration (CMC) was 1.4 x 10(-5) mol L-1. The pH-sensitivity was confirmed in vitro through a drug release assay. Cytotoxicity studies confirmed that the encapsulation of DOX into the micelles did not impair the drug cytotoxic activity. Moreover, the incorporation of DSPE-PEG2000-DTPA into the micelles allowed it radio-labeling with the technetium-99 m in high yield and stability, permitting its use to monitor antitumor therapy. In this sense, the pH-sensitive micelles were able to inhibit tumor growth significantly when compared to non-pH-sensitive micelles and the free drug. in vivo toxicity evaluation in the zebrafish model revealed significantly lower toxicity of pH-sensitive micelles compared to the free drug. These results indicate that the developed formulation presents itself as a promising alternative to potentiate the treatment of tumors.
Palavras-chave
Micelles, pH-sensitivity, Doxorubicin, Antitumor, Drug delivery
URI
https://observatorio.fm.usp.br/handle/OPI/40041
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Coleções
Artigos e Materiais de Revistas Científicas - FM/Outros
Artigos e Materiais de Revistas Científicas - ODS/03