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Title: Toxicological study of a new doxorubicin-loaded pH-sensitive liposome : a preclinical approach.
Authors: Silva, Juliana de Oliveira
Miranda, Sued Eustaquio Mendes
Leite, Elaine Amaral
Sabino, Adriano de Paula
Borges, Karina Braga Gomes
Cardoso, Valbert Nascimento
Cassali, Geovanni Dantas
Guimarães, Andrea Grabe
Oliveira, Mônica Cristina de
Barros, André Luís Branco de
Keywords: Doxorubicin
Acute toxicity
Issue Date: 2018
Citation: SILVA, J. de O. et al. Toxicological study of a new doxorubicin-loaded pH-sensitive liposome : a preclinical approach. Toxicology and Applied Pharmacology, v. 352, p. 162-169, ago. 2018. Disponível em: <>. Acesso em: 25 fev. 2019.
Abstract: Doxorubicin (DOX) is widely used in cancer treatment, however, the use of this drug is often limited due to its cardiotoxic side effects. In order to avoid these adverse effects, the encapsulation of DOX into nanosystems has been used in the last decades. In this context, pH-sensitive liposomes have been shown promising for delivering cytotoxic agents into tumor cells, however, the lack of information about in vivo toxicity of this nanocarrier has impaired translational studies. Therefore, the aim of this work was to investigate the acute toxicity and cardiotoxicity of DOX-loading pH-sensitive liposomes (SpHL-DOX). To achieve this, female BALB/c mice, after intravenous administration, were monitored by means of clinical, laboratory, histopathological and electrocardiographic (ECG) analyses. Results indicate that SpHL was able to prevent renal toxicity and the hepatic injury was less extensive than free DOX. In addition, lower body weight loss was associated with less ECG QT interval prolongation to animals receiving SpHL-DOX (14.6 ± 5.2%) compared to animals receiving free DOX (35.7 ± 4.0%) or non-pH-sensitive liposomes (nSpHL-DOX) (47.0 ± 9.8%). These results corroborate with SpHL-DOX biodistribution studies published by our group. In conclusion, the SpHL-DOX showed less toxic effects on mice compared to free DOX or nSpHL-DOX indicating that SpHL-DOX is a promising strategy to reduce the serious cardiotoxic effects of DOX.
ISSN: 0041008X
Appears in Collections:DEFAR - Artigos publicados em periódicos

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