Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/11441
Title: Antitumor effectiveness and toxicity of cisplatin-loaded long-circulating and pH-sensitive liposomes against Ehrlich ascitic tumor
Authors: Maroni, Laís de Carvalho
Silveira, Amanda Cardoso de Oliveira
Leite, Elaine Amaral
Melo, Marília Martins
Ribeiro, Ana Flávia de Carvalho
Cassali, Geovani Dantas
Souza, Cristina Maria de
Fagundes, Elaine Maria de Souza
Caldas, Iramaya Rodrigues
Araújo, Márcio Sobreira Silva
Martins Filho, Olindo Assis
Oliveira, Mônica Cristina de
Carvalho, Andréa Teixeira de
Affilliation: Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Biomarcadores de Diagnóstico e Monitoração. Belo Horizonte, MG, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Biomarcadores de Diagnóstico e Monitoração. Belo Horizonte, MG, Brasil
Universidade Federal de Minas Gerais. Faculdade de Farmácia. Departamento de Produtos Farmacêuticos. Belo Horizonte, MG, Brasil
Universidade Federal de Minas Gerais. Escola de Veterinária. Departamento de Clínica e Cirurgia. Belo Horizonte, MG, Brasil
Universidade Federal de Minas Gerais. Escola de Veterinária. Departamento de Clínica e Cirurgia. Belo Horizonte, MG, Brasil/ Universidade Estadual de Santa Cruz. Departamento de Ciências Agrárias e Ambientais. Ilhéus, BA, Brasil
Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Patologia Geral. Laboratório de Patologia Comparada. Belo Horizonte, MG, Brasil
Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Patologia Geral. Laboratório de Patologia Comparada. Belo Horizonte, MG, Brasil
Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Fisiologia e Biofísica. Belo Horizonte, MG, Brasil
Fundação Oswaldo Cruz. Brasília, DF, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Biomarcadores de Diagnóstico e Monitoração. Belo Horizonte, MG, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Biomarcadores de Diagnóstico e Monitoração. Belo Horizonte, MG, Brasil
Universidade Federal de Minas Gerais. Faculdade de Farmácia. Departamento de Produtos Farmacêuticos. Belo Horizonte, MG, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Biomarcadores de Diagnóstico e Monitoração. Belo Horizonte, MG, Brasil
Abstract: Cisplatin (CDDP) is one of the most active cytotoxic agents commonly used in the treatment of peritoneal carcinomatosis. The disadvantages of its clinical use are systemic side-effects, such as nephrotoxicity and myelotoxicity. Long-circulating and pH-sensitive liposomes containing CDDP (SpHL-CDDP) were developed by our research group aiming to promote the release of CDDP near the tumor as well as decreasing toxicity. The aim of this study was to evaluate the antitumor efficacy and toxicity of SpHL-CDDP after intraperitoneal administration in initial or disseminated tumor-bearing mice, at a dose of 12 mg/kg. The survival was monitored and blood samples were collected for biochemical and hematological analysis. Kidneys, liver and spleen were removed for histopathological examination. Tumor cells were evaluated for cellular viability and cell cycle. The survival of animals treated with SpHL-CDDP was higher than those treated with free CDDP. The cell death caused by treatment with SpHL-CDDP occurred through induction of apoptosis, with a cell cycle arrest at the G0/G1 phase. The treatment of mice presenting initial cancer with both formulations provoked a suppression of granulocytes. Mice treated with free CDDP also showed a decrease in platelet count, which suggests a high myelotoxicity. In an advanced cancer model, SpHL-CDDP treatment allowed an improvement of the immune response. Mice affected by cancer at an early stage and treated with free CDDP or SpHL-CDDP showed a lower urea/creatinine index compared with the saline control group. These findings indicate that both treatments were able to reduce the renal damage caused by peritoneal carcinomatosis. Microscopic analysis of kidneys from mice treated with SpHL-CDDP showed a discrete morphological alteration, while tubular necrosis was observed for free CDDP-treated mice. Concerning hepatotoxicity, no alteration in clinical chemistry parameters was observed. These findings reveal that SpHL-CDDP can improve the antitumor efficacy and decrease renal and bone marrow toxicity.
Keywords: long-circulating and pH-sensitive liposomes
cisplatin
antitumor effectiveness
intraperitoneal
Ehrlich ascitic tumor
Issue Date: 2012
Publisher: The Society for Experimental Biology and Medicine
Citation: MARONI, Laís de Carvalho et al. Antitumor effectiveness and toxicity of cisplatin-loaded long-circulating and pH-sensitive liposomes against Ehrlich ascitic tumor. Experimental Biology and Medicine, vol.237, n. 8, p. 973-984, 2012
DOI: 10.1258/ebm.2012.011432
ISSN: 1535-3702
Copyright: restricted access
Appears in Collections:MG - IRR - Artigos de Periódicos

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