Author | Araujo, Jose Geraldo Coimbra | |
Author | Mota, Luciene das Graças | |
Author | Leite, Elaine Amaral | |
Author | Maroni, Laís de Carvalho | |
Author | Wainstein, Alberto Julius Alves | |
Author | Coelho, Luiz Gonzaga Vaz | |
Author | Savassi-Rocha | |
Author | Pereira, Márcio Tadeu | |
Author | Carvalho, Andréa Teixeira de | |
Author | Cardoso, Valbert Nascimento | |
Author | Oliveira, Mônica Cristina De | |
Access date | 2023-07-25T14:40:07Z | |
Available date | 2023-07-25T14:40:07Z | |
Document date | 2011 | |
Citation | ARAÚJO, José Geraldo Coimbra et al. Biodistribution and antitumoral effect of long-circulating and pH-sensitive liposomal cisplatin administered in Ehrlich tumor-bearing mice. Exp Biol Med., v. 236, n. 7, p. 808-815. 2011. doi: 10.1258/ebm.2011.011038. | en_US |
ISSN | 1535-3702 | en_US |
URI | https://www.arca.fiocruz.br/handle/icict/59748 | |
Language | eng | en_US |
Publisher | SAGE Publications | en_US |
Rights | restricted access | en_US |
Title | Biodistribution and antitumoral effect of long-circulating and pH-sensitive liposomal cisplatin administered in Ehrlich tumor-bearing mice | en_US |
Type | Article | en_US |
DOI | 10.1258/ebm.2011.011038 | |
Abstract | Cisplatin (CDDP) is one of the most active cytotoxic agents and has been widely used in the treatment of peritoneal carcinomatosis by the intraperitoneal (i.p.) route. However, CDDP, a low-molecular-weight compound, is rapidly absorbed by the capillaries in the i.p. serosa and transferred to the bloodstream, inducing the appearance of systemic side-effects, such as nephrotoxicity. Furthermore, the i.p. CDDP chemotherapy is limited to patients whose residual tumor nodules are less than 0.5 cm in diameter after surgical debulking. The failure of i.p. therapy is attributed to the poor penetration of CDDP into larger tumors. One strategy to improve drug delivery in the peritoneal region and reduce toxicity is the use of drug delivery systems. The objective of the present work was to evaluate the biodistribution and antitumoral effect of long-circulating and pH-sensitive liposomes containing COOP (SpHL-CDDP), as compared with free CDDP, after their i.p. administration in Ehrlich ascitic tumor-bearing mice. After administering a 6 mg/kg single i.p. bolus injection of either free CDDP or SpHL-CDDP, ascitic fluid (AF), blood and organs (kidneys, liver, spleen and lungs) were collected and analyzed for CDDP content. The area under the CDDP concentration-time curve (AUC) obtained for AF and blood after SpHL-CDDP administration was 3.3-fold larger and 1.3-fold lower, respectively, when compared with free COOP treatment, thus indicating its high retention within the peritoneal cavity. The determination of the ratio between AUC in each tissue and that in blood (Kp) showed a lower accumulation of COOP in kidneys after SpHL-COOP treatment. The SpHL-COOP treatment demonstrated a significant uptake by the liver and spleen. SpHL-COOP treatment led to a higher survival rate of mice with initial or disseminated peritoneal carcinomatosis than COOP treatment. These results indicate that SpHL-CDDP may be useful for i.p. chemotherapy due to their greater concentration in the peritoneal cavity | en_US |
Affilliation | Universidade Federal de Minas Gerais. Departamento de Produtos Farmacêuticos. Belo Horizonte, MG, Brazil | en_US |
Affilliation | Universidade Federal de Minas Gerais. Faculdade de Farmácia. Departamento de Análises Clínicas. Belo Horizonte, MG, Brazil | en_US |
Affilliation | Universidade Federal de Minas Gerais. Departamento de Produtos Farmacêuticos. Belo Horizonte, MG, Brazil/Federal dos Vales do Jequitinhonha e Mucuri. Faculdade de Ciências Biológicas e da Saúde. Departamento de Farmácia. Universidade. Diamantina, MG, Brasil | en_US |
Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Biomarcadores de Diagnóstico e Monitoração. Belo Horizonte, MG, Brazil | en_US |
Affilliation | Universidade Federal de Minas Gerais. Hospital das Clínicas. Instituto Alfa de Gastroenterologia. Belo Horizonte, MG, Brazil | en_US |
Affilliation | Universidade Federal de Minas Gerais. Hospital das Clínicas. Instituto Alfa de Gastroenterologia. Belo Horizonte, MG, Brazil | en_US |
Affilliation | Universidade Federal de Minas Gerais. Hospital das Clínicas. Instituto Alfa de Gastroenterologia. Belo Horizonte, MG, Brazil | en_US |
Affilliation | Centro de Desenvolvimento de Tecnologia Nuclear. Comissão Nacional de Energia. Belo Horizonte, MG, Brazil | en_US |
Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Biomarcadores de Diagnóstico e Monitoração. Belo Horizonte, MG, Brazil | en_US |
Affilliation | Universidade Federal de Minas Gerais. Faculdade de Farmácia. Departamento de Análises Clínicas. Belo Horizonte, MG, Brazil | en_US |
Affilliation | Universidade Federal de Minas Gerais. Departamento de Produtos Farmacêuticos. Belo Horizonte, MG, Brazil | en_US |
Subject | ancer | en_US |
Subject | liposomes | en_US |
Subject | cisplatin | en_US |
Subject | biodistribution | en_US |
Subject | pharmacokinetics | en_US |
Subject | antitumoral effect | en_US |
Embargo date | 3100-12-31 | |