Intramyocardial sustained delivery of placental growth factor using nanoparticles as a vehicle for delivery in the rat infarct model

Ziyad Mohammed Binsalamah1, Arghya Paul2, Afshan Afsar Khan2, Satya Prakash2, Dominique Shum-Tim11Divisions of Cardiac Surgery and Surgical Research, McGill University Health Center, 2Biomedical Technology and Cell Therapy Research Laboratory, Department of Biomedical Engineering, Faculty of Medicin...

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Autores principales:	Shum-Tim D, Prakash S, Khan AA, Paul A, Binsalamah ZM
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2011
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/63279ff4eb2948d9815d177f692b37b9
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spelling	oai:doaj.org-article:63279ff4eb2948d9815d177f692b37b92021-12-02T07:46:15ZIntramyocardial sustained delivery of placental growth factor using nanoparticles as a vehicle for delivery in the rat infarct model1176-91141178-2013https://doaj.org/article/63279ff4eb2948d9815d177f692b37b92011-10-01T00:00:00Zhttp://www.dovepress.com/intramyocardial-sustained-delivery-of-placental-growth-factor-using-na-a8568https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Ziyad Mohammed Binsalamah1, Arghya Paul2, Afshan Afsar Khan2, Satya Prakash2, Dominique Shum-Tim11Divisions of Cardiac Surgery and Surgical Research, McGill University Health Center, 2Biomedical Technology and Cell Therapy Research Laboratory, Department of Biomedical Engineering, Faculty of Medicine, McGill University, Montreal, Quebec, CanadaBackground: Acute myocardial ischemia results in scar formation with ventricular dilatation and eventually heart failure. Placental growth factor (PlGF) is reported to stimulate angiogenesis and improve cardiac function. In this study, it was hypothesized that intramyocardial injection of PlGF contained in nanoparticles can be released at the site of action for an extended time period as a sustained slow-release protective mechanism that accelerates myocardial recovery in a rat model of ischemic cardiomyopathy.Methods: PlGF-loaded chitosan-alginate nanoparticles were injected into an acute myocardial infarction model in rats (n = 10 per group). Transthoracic echocardiography was performed at different time intervals. Enzyme-linked immunosorbent assay was used to measure the serum cytokines levels at 8 weeks. Hearts were stained with Masson&#39;s trichrome for scar area analysis. Immunofluorostaining was performed to evaluate the extent of myocardial angiogenesis at the infarction border. PlGF enzyme-linked immunosorbent assay was used to measure the in vitro release kinetics of PlGF-loaded nanoparticles.Results: At 8 weeks after coronary ligation, hearts that were treated with PlGF-loaded chitosan-alginate nanoparticles had significant increases in left-ventricular function (P &lt; 0.01), vascular density (P &lt; 0.01), and in the serum level of the anti-inflammatory cytokine interleukin-10 (P &lt; 0.05). There was significant decrease in scar area formation (P &lt; 0.05) and in serum levels of the proinflammatory cytokines tumor necrosis factor-alpha and interleukin-6 (P &lt; 0.01). In vitro PlGF-release kinetic studies showed a sustained release of PlGF from the particles over a 120-hour period.Conclusion: The use of nanoparticles as a vehicle for PlGF delivery, as opposed to the direct injection of the growth factor after acute myocardial infarction, can provide sustained slow-release PlGF therapy, enhancing the positive effects of the growth factor in the setting of acute myocardial ischemia.Keywords: nanotechnology, serum cytokines, myocardial therapy, angiogenesis, regenerative medicineShum-Tim DPrakash SKhan AAPaul ABinsalamah ZMDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2011, Iss default, Pp 2667-2678 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Shum-Tim D Prakash S Khan AA Paul A Binsalamah ZM Intramyocardial sustained delivery of placental growth factor using nanoparticles as a vehicle for delivery in the rat infarct model
description	Ziyad Mohammed Binsalamah1, Arghya Paul2, Afshan Afsar Khan2, Satya Prakash2, Dominique Shum-Tim11Divisions of Cardiac Surgery and Surgical Research, McGill University Health Center, 2Biomedical Technology and Cell Therapy Research Laboratory, Department of Biomedical Engineering, Faculty of Medicine, McGill University, Montreal, Quebec, CanadaBackground: Acute myocardial ischemia results in scar formation with ventricular dilatation and eventually heart failure. Placental growth factor (PlGF) is reported to stimulate angiogenesis and improve cardiac function. In this study, it was hypothesized that intramyocardial injection of PlGF contained in nanoparticles can be released at the site of action for an extended time period as a sustained slow-release protective mechanism that accelerates myocardial recovery in a rat model of ischemic cardiomyopathy.Methods: PlGF-loaded chitosan-alginate nanoparticles were injected into an acute myocardial infarction model in rats (n = 10 per group). Transthoracic echocardiography was performed at different time intervals. Enzyme-linked immunosorbent assay was used to measure the serum cytokines levels at 8 weeks. Hearts were stained with Masson&#39;s trichrome for scar area analysis. Immunofluorostaining was performed to evaluate the extent of myocardial angiogenesis at the infarction border. PlGF enzyme-linked immunosorbent assay was used to measure the in vitro release kinetics of PlGF-loaded nanoparticles.Results: At 8 weeks after coronary ligation, hearts that were treated with PlGF-loaded chitosan-alginate nanoparticles had significant increases in left-ventricular function (P &lt; 0.01), vascular density (P &lt; 0.01), and in the serum level of the anti-inflammatory cytokine interleukin-10 (P &lt; 0.05). There was significant decrease in scar area formation (P &lt; 0.05) and in serum levels of the proinflammatory cytokines tumor necrosis factor-alpha and interleukin-6 (P &lt; 0.01). In vitro PlGF-release kinetic studies showed a sustained release of PlGF from the particles over a 120-hour period.Conclusion: The use of nanoparticles as a vehicle for PlGF delivery, as opposed to the direct injection of the growth factor after acute myocardial infarction, can provide sustained slow-release PlGF therapy, enhancing the positive effects of the growth factor in the setting of acute myocardial ischemia.Keywords: nanotechnology, serum cytokines, myocardial therapy, angiogenesis, regenerative medicine
format	article
author	Shum-Tim D Prakash S Khan AA Paul A Binsalamah ZM
author_facet	Shum-Tim D Prakash S Khan AA Paul A Binsalamah ZM
author_sort	Shum-Tim D
title	Intramyocardial sustained delivery of placental growth factor using nanoparticles as a vehicle for delivery in the rat infarct model
title_short	Intramyocardial sustained delivery of placental growth factor using nanoparticles as a vehicle for delivery in the rat infarct model
title_full	Intramyocardial sustained delivery of placental growth factor using nanoparticles as a vehicle for delivery in the rat infarct model
title_fullStr	Intramyocardial sustained delivery of placental growth factor using nanoparticles as a vehicle for delivery in the rat infarct model
title_full_unstemmed	Intramyocardial sustained delivery of placental growth factor using nanoparticles as a vehicle for delivery in the rat infarct model
title_sort	intramyocardial sustained delivery of placental growth factor using nanoparticles as a vehicle for delivery in the rat infarct model
publisher	Dove Medical Press
publishDate	2011
url	https://doaj.org/article/63279ff4eb2948d9815d177f692b37b9
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Intramyocardial sustained delivery of placental growth factor using nanoparticles as a vehicle for delivery in the rat infarct model

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