Delivery as nanoparticles reduces imatinib mesylate-induced cardiotoxicity and improves anticancer activity
Autor(a) principal: | |
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Data de Publicação: | 2015 |
Outros Autores: | , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/1822/40255 |
Resumo: | Clinical effectiveness of imatinib mesylate in cancer treatment is compromised by its off-target cardiotoxicity. In the present study, we have developed physically stable imatinib mesylate-loaded poly(lactide-co-glycolide) nanoparticles (INPs) that could sustainably release the drug, and studied its efficacy by in vitro anticancer and in vivo cardiotoxicity assays. MTT (methylthiazolyldiphenyl-tetrazolium bromide) assay revealed that INPs are more cytotoxic to MCF-7 breast cancer cells compared to the equivalent concentration of free imatinib mesylate. Wistar rats orally administered with 50 mg/kg INPs for 28 days showed no significant cardiotoxicity or associated changes. Whereas, increased alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase levels, and reduced white blood cell, red blood cell, and hemoglobin content were observed in the animals administered with free drug. While the histological sections from hearts of animals that received INPs did not show any significant cardiotoxic symptoms, loss of normal architecture and increased cytoplasmic vacuolization were observed in the heart sections of animals administered with free imatinib mesylate. Based on these results, we conclude that nano-encapsulation of imatinib mesylate increases its efficacy against cancer cells, with almost no cardiotoxicity. |
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Delivery as nanoparticles reduces imatinib mesylate-induced cardiotoxicity and improves anticancer activityImatinib nanoparticlesCytotoxicityCardiotoxicityHematologyScience & TechnologyClinical effectiveness of imatinib mesylate in cancer treatment is compromised by its off-target cardiotoxicity. In the present study, we have developed physically stable imatinib mesylate-loaded poly(lactide-co-glycolide) nanoparticles (INPs) that could sustainably release the drug, and studied its efficacy by in vitro anticancer and in vivo cardiotoxicity assays. MTT (methylthiazolyldiphenyl-tetrazolium bromide) assay revealed that INPs are more cytotoxic to MCF-7 breast cancer cells compared to the equivalent concentration of free imatinib mesylate. Wistar rats orally administered with 50 mg/kg INPs for 28 days showed no significant cardiotoxicity or associated changes. Whereas, increased alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase levels, and reduced white blood cell, red blood cell, and hemoglobin content were observed in the animals administered with free drug. While the histological sections from hearts of animals that received INPs did not show any significant cardiotoxic symptoms, loss of normal architecture and increased cytoplasmic vacuolization were observed in the heart sections of animals administered with free imatinib mesylate. Based on these results, we conclude that nano-encapsulation of imatinib mesylate increases its efficacy against cancer cells, with almost no cardiotoxicity.GM and CJS were supported by the Fundação para a Ciência e a Tecnologia (FCT), Portugal, by grants SFRH/ BD/72809/2010 and SFRH/BPD/89493/2012, respectively. The present work was also supported by the FCT projects PTDC/AGR-GPL/119211/2010 and UID/AGR/04033/2013.Dove Press LtdUniversidade do MinhoMarslin, GregoryRevina, Ann MaryKhandelwal, Vinoth Kumar MegrajBalakumar, KrishnamoorthyPrakash, JoseFranklin, GregorySheeba, Caroline J.20152015-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/1822/40255engMarslin, G., Revina, A. M., Khandelwal, V. K. M., Balakumar, K., Prakash, J., Franklin, G., & Sheeba, C. J. (2015). Delivery as nanoparticles reduces imatinib mesylate-induced cardiotoxicity and improves anticancer activity. International Journal of Nanomedicine, 10, 3163-3170. doi: 10.2147/ijn.s759621178-201310.2147/IJN.S7596225995626https://www.dovepress.com/delivery-as-nanoparticles-reduces-imatinib-mesylate-induced-cardiotoxi-peer-reviewed-article-IJNinfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-21T12:24:57Zoai:repositorium.sdum.uminho.pt:1822/40255Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T19:19:07.610418Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Delivery as nanoparticles reduces imatinib mesylate-induced cardiotoxicity and improves anticancer activity |
title |
Delivery as nanoparticles reduces imatinib mesylate-induced cardiotoxicity and improves anticancer activity |
spellingShingle |
Delivery as nanoparticles reduces imatinib mesylate-induced cardiotoxicity and improves anticancer activity Marslin, Gregory Imatinib nanoparticles Cytotoxicity Cardiotoxicity Hematology Science & Technology |
title_short |
Delivery as nanoparticles reduces imatinib mesylate-induced cardiotoxicity and improves anticancer activity |
title_full |
Delivery as nanoparticles reduces imatinib mesylate-induced cardiotoxicity and improves anticancer activity |
title_fullStr |
Delivery as nanoparticles reduces imatinib mesylate-induced cardiotoxicity and improves anticancer activity |
title_full_unstemmed |
Delivery as nanoparticles reduces imatinib mesylate-induced cardiotoxicity and improves anticancer activity |
title_sort |
Delivery as nanoparticles reduces imatinib mesylate-induced cardiotoxicity and improves anticancer activity |
author |
Marslin, Gregory |
author_facet |
Marslin, Gregory Revina, Ann Mary Khandelwal, Vinoth Kumar Megraj Balakumar, Krishnamoorthy Prakash, Jose Franklin, Gregory Sheeba, Caroline J. |
author_role |
author |
author2 |
Revina, Ann Mary Khandelwal, Vinoth Kumar Megraj Balakumar, Krishnamoorthy Prakash, Jose Franklin, Gregory Sheeba, Caroline J. |
author2_role |
author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade do Minho |
dc.contributor.author.fl_str_mv |
Marslin, Gregory Revina, Ann Mary Khandelwal, Vinoth Kumar Megraj Balakumar, Krishnamoorthy Prakash, Jose Franklin, Gregory Sheeba, Caroline J. |
dc.subject.por.fl_str_mv |
Imatinib nanoparticles Cytotoxicity Cardiotoxicity Hematology Science & Technology |
topic |
Imatinib nanoparticles Cytotoxicity Cardiotoxicity Hematology Science & Technology |
description |
Clinical effectiveness of imatinib mesylate in cancer treatment is compromised by its off-target cardiotoxicity. In the present study, we have developed physically stable imatinib mesylate-loaded poly(lactide-co-glycolide) nanoparticles (INPs) that could sustainably release the drug, and studied its efficacy by in vitro anticancer and in vivo cardiotoxicity assays. MTT (methylthiazolyldiphenyl-tetrazolium bromide) assay revealed that INPs are more cytotoxic to MCF-7 breast cancer cells compared to the equivalent concentration of free imatinib mesylate. Wistar rats orally administered with 50 mg/kg INPs for 28 days showed no significant cardiotoxicity or associated changes. Whereas, increased alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase levels, and reduced white blood cell, red blood cell, and hemoglobin content were observed in the animals administered with free drug. While the histological sections from hearts of animals that received INPs did not show any significant cardiotoxic symptoms, loss of normal architecture and increased cytoplasmic vacuolization were observed in the heart sections of animals administered with free imatinib mesylate. Based on these results, we conclude that nano-encapsulation of imatinib mesylate increases its efficacy against cancer cells, with almost no cardiotoxicity. |
publishDate |
2015 |
dc.date.none.fl_str_mv |
2015 2015-01-01T00:00:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/1822/40255 |
url |
http://hdl.handle.net/1822/40255 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Marslin, G., Revina, A. M., Khandelwal, V. K. M., Balakumar, K., Prakash, J., Franklin, G., & Sheeba, C. J. (2015). Delivery as nanoparticles reduces imatinib mesylate-induced cardiotoxicity and improves anticancer activity. International Journal of Nanomedicine, 10, 3163-3170. doi: 10.2147/ijn.s75962 1178-2013 10.2147/IJN.S75962 25995626 https://www.dovepress.com/delivery-as-nanoparticles-reduces-imatinib-mesylate-induced-cardiotoxi-peer-reviewed-article-IJN |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Dove Press Ltd |
publisher.none.fl_str_mv |
Dove Press Ltd |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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1799132648499576832 |