Delivery as nanoparticles reduces imatinib mesylate-induced cardiotoxicity and improves anticancer activity

Gregory Marslin,1 Ann Mary Revina,2,3 Vinoth Kumar Megraj Khandelwal,4 Krishnamoorthy Balakumar,5 Jose Prakash,6 Gregory Franklin,1,* Caroline J Sheeba2,3,7,*1AgroBioPlant Group, Centre for the Research and Technology of Agro-Environment and Biological Sciences (CITAB), University of Minho, Braga, P...

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Autores principales:	Marslin G, Revina AM, Khandelwal VKM, Balakumar K, Prakash J, Franklin G, Sheeba CJ
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2015
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/ca3682a6eef24e259b3fb696eeced387
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spelling	oai:doaj.org-article:ca3682a6eef24e259b3fb696eeced3872021-12-02T00:10:20ZDelivery as nanoparticles reduces imatinib mesylate-induced cardiotoxicity and improves anticancer activity1178-2013https://doaj.org/article/ca3682a6eef24e259b3fb696eeced3872015-04-01T00:00:00Zhttp://www.dovepress.com/delivery-as-nanoparticles-reduces-imatinib-mesylate-induced-cardiotoxi-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Gregory Marslin,1 Ann Mary Revina,2,3 Vinoth Kumar Megraj Khandelwal,4 Krishnamoorthy Balakumar,5 Jose Prakash,6 Gregory Franklin,1,* Caroline J Sheeba2,3,7,1AgroBioPlant Group, Centre for the Research and Technology of Agro-Environment and Biological Sciences (CITAB), University of Minho, Braga, Portugal; 2Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal; 3ICVS/3B’s – PT Government Associate Laboratory, Braga/Guimarães, Portugal; 4Department of Translational Pharmacology, Consorzio Mario Negri Sud, Santa Maria Imbaro, Italy; 5Department of Pharmaceutics, PSG College of Pharmacy, Coimbatore, Tamil Nadu, India; 6Department of Pharmaceutics, Vels University, Chennai, Tamil Nadu, India; 7Regenerative Medicine Program, Department of Biomedical Sciences and Medicine, University of Algarve, Faro, PortugalThese authors contributed equally to this workAbstract: 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.Keywords: imatinib nanoparticles, cytostoxicity, cardiotoxicity, hematologyMarslin GRevina AMKhandelwal VKMBalakumar KPrakash JFranklin GSheeba CJDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2015, Iss default, Pp 3163-3170 (2015)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Marslin G Revina AM Khandelwal VKM Balakumar K Prakash J Franklin G Sheeba CJ Delivery as nanoparticles reduces imatinib mesylate-induced cardiotoxicity and improves anticancer activity
description	Gregory Marslin,1 Ann Mary Revina,2,3 Vinoth Kumar Megraj Khandelwal,4 Krishnamoorthy Balakumar,5 Jose Prakash,6 Gregory Franklin,1,* Caroline J Sheeba2,3,7,1AgroBioPlant Group, Centre for the Research and Technology of Agro-Environment and Biological Sciences (CITAB), University of Minho, Braga, Portugal; 2Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal; 3ICVS/3B’s – PT Government Associate Laboratory, Braga/Guimarães, Portugal; 4Department of Translational Pharmacology, Consorzio Mario Negri Sud, Santa Maria Imbaro, Italy; 5Department of Pharmaceutics, PSG College of Pharmacy, Coimbatore, Tamil Nadu, India; 6Department of Pharmaceutics, Vels University, Chennai, Tamil Nadu, India; 7Regenerative Medicine Program, Department of Biomedical Sciences and Medicine, University of Algarve, Faro, PortugalThese authors contributed equally to this workAbstract: 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.Keywords: imatinib nanoparticles, cytostoxicity, cardiotoxicity, hematology
format	article
author	Marslin G Revina AM Khandelwal VKM Balakumar K Prakash J Franklin G Sheeba CJ
author_facet	Marslin G Revina AM Khandelwal VKM Balakumar K Prakash J Franklin G Sheeba CJ
author_sort	Marslin G
title	Delivery as nanoparticles reduces imatinib mesylate-induced cardiotoxicity and improves anticancer activity
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
publisher	Dove Medical Press
publishDate	2015
url	https://doaj.org/article/ca3682a6eef24e259b3fb696eeced387
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Delivery as nanoparticles reduces imatinib mesylate-induced cardiotoxicity and improves anticancer activity

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