Antitumor effectiveness and toxicity of cisplatin-loaded long-circulating and pH-sensitive liposomes against Ehrlich ascitic tumor

dc.creatorMaroni, Laís de Carvalho
dc.creatorSilveira, Amanda Cardoso de Oliveira
dc.creatorLeite, Elaine Amaral
dc.creatorMelo, Marília Martins
dc.creatorRibeiro, Ana Flávia de Carvalho
dc.creatorCassali, Geovani Dantas
dc.creatorSouza, Cristina Maria de
dc.creatorFagundes, Elaine Maria de Souza
dc.creatorCaldas, Iramaya Rodrigues
dc.creatorAraújo, Márcio Sobreira Silva
dc.creatorMartins Filho, Olindo Assis
dc.creatorOliveira, Mônica Cristina de
dc.creatorCarvalho, Andréa Teixeira de
dc.date2015-08-12T18:01:21Z
dc.date2015-08-12T18:01:21Z
dc.date2012
dc.date.accessioned2023-09-26T21:57:45Z
dc.date.available2023-09-26T21:57:45Z
dc.identifierMARONI, 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
dc.identifier1535-3702
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/11441
dc.identifier10.1258/ebm.2012.011432
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8874190
dc.descriptionCisplatin (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.
dc.formatapplication/pdf
dc.languageeng
dc.publisherThe Society for Experimental Biology and Medicine
dc.rightsrestricted access
dc.subjectlong-circulating and pH-sensitive liposomes
dc.subjectcisplatin
dc.subjectantitumor effectiveness
dc.subjectintraperitoneal
dc.subjectEhrlich ascitic tumor
dc.titleAntitumor effectiveness and toxicity of cisplatin-loaded long-circulating and pH-sensitive liposomes against Ehrlich ascitic tumor
dc.typeArticle


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