Starch nanoparticles for delivery of the histone deacetylase inhibitor CG-1521 in breast cancer treatment

Esma Alp,1–4 Fehmi Damkaci,2 Eylem Guven,1 Martin Tenniswood3,4 1Department of Nanotechnology and Nanomedicine, Hacettepe University, Beytepe, Ankara 06800, Turkey; 2Department of Chemistry, State University of New York at Oswego, Oswego, NY 13126, USA; 3Cancer Research Center, Rensselaer...

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Autores principales:	Alp E, Damkaci F, Guven E, Tenniswood M
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2019
Materias:	cell cycle apoptosis DNA fragmentation CG-1521 MCF-7 Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/0c1ed394cb96489eb89ecd40836a2479
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spelling	oai:doaj.org-article:0c1ed394cb96489eb89ecd40836a24792021-12-02T08:19:07ZStarch nanoparticles for delivery of the histone deacetylase inhibitor CG-1521 in breast cancer treatment1178-2013https://doaj.org/article/0c1ed394cb96489eb89ecd40836a24792019-02-01T00:00:00Zhttps://www.dovepress.com/starch-nanoparticles-for-delivery-of-the-histone-deacetylase-inhibitor-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Esma Alp,1–4 Fehmi Damkaci,2 Eylem Guven,1 Martin Tenniswood3,4 1Department of Nanotechnology and Nanomedicine, Hacettepe University, Beytepe, Ankara 06800, Turkey; 2Department of Chemistry, State University of New York at Oswego, Oswego, NY 13126, USA; 3Cancer Research Center, Rensselaer, NY 12144, USA; 4Department of Biomedical Sciences, State University of New York, University at Albany, Rensselaer, NY 12144, USA Background: The efficacy of epigenetic drugs, such as histone deacetylase inhibitors, is often diminished by poor aqueous solubility resulting in limited bioavailability and a low therapeutic index. To overcome the suboptimal therapeutic index, we have developed a biocompatible starch nanoparticle formulation of CG-1521, a histone deacetylase inhibitor in preclinical development for hard-to-treat breast cancers, which improves its bioavailability and half-life. Methods: The physicochemical parameters (size, zeta potential, morphology, loading, and release kinetics) of these nanoparticles (CG-NPs) have been optimized and their cytotoxic and apoptotic capacities measured in MCF-7 breast cancer cell line. The mechanism of action of the encapsulated drug was compared with the free drug at molecular level. Results: We show that encapsulation of CG-1521 substantially reduces the release rate of drug and provides a significantly enhanced cytotoxic ability of nanoparticles compared with equivalent dose of free CG-1521. CG-NPs induced cell cycle arrest and significant apoptosis in MCF-7 cells in vitro. The biological action of encapsulated drug has the similar impact with free drug on gene expression.Conclusion: The findings suggest that encapsulation of CG-1521 into starch nanoparticles can improve drug delivery of histone deacetylase inhibitors for breast cancer therapy without interfering with the mechanism of action of the drug. Keywords: cell cycle, apoptosis, DNA fragmentation, gene expression, epigenetics, MCF-7  Alp EDamkaci FGuven ETenniswood MDove Medical Pressarticlecell cycleapoptosisDNA fragmentationCG-1521MCF-7Medicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 14, Pp 1335-1346 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	cell cycle apoptosis DNA fragmentation CG-1521 MCF-7 Medicine (General) R5-920
spellingShingle	cell cycle apoptosis DNA fragmentation CG-1521 MCF-7 Medicine (General) R5-920 Alp E Damkaci F Guven E Tenniswood M Starch nanoparticles for delivery of the histone deacetylase inhibitor CG-1521 in breast cancer treatment
description	Esma Alp,1–4 Fehmi Damkaci,2 Eylem Guven,1 Martin Tenniswood3,4 1Department of Nanotechnology and Nanomedicine, Hacettepe University, Beytepe, Ankara 06800, Turkey; 2Department of Chemistry, State University of New York at Oswego, Oswego, NY 13126, USA; 3Cancer Research Center, Rensselaer, NY 12144, USA; 4Department of Biomedical Sciences, State University of New York, University at Albany, Rensselaer, NY 12144, USA Background: The efficacy of epigenetic drugs, such as histone deacetylase inhibitors, is often diminished by poor aqueous solubility resulting in limited bioavailability and a low therapeutic index. To overcome the suboptimal therapeutic index, we have developed a biocompatible starch nanoparticle formulation of CG-1521, a histone deacetylase inhibitor in preclinical development for hard-to-treat breast cancers, which improves its bioavailability and half-life. Methods: The physicochemical parameters (size, zeta potential, morphology, loading, and release kinetics) of these nanoparticles (CG-NPs) have been optimized and their cytotoxic and apoptotic capacities measured in MCF-7 breast cancer cell line. The mechanism of action of the encapsulated drug was compared with the free drug at molecular level. Results: We show that encapsulation of CG-1521 substantially reduces the release rate of drug and provides a significantly enhanced cytotoxic ability of nanoparticles compared with equivalent dose of free CG-1521. CG-NPs induced cell cycle arrest and significant apoptosis in MCF-7 cells in vitro. The biological action of encapsulated drug has the similar impact with free drug on gene expression.Conclusion: The findings suggest that encapsulation of CG-1521 into starch nanoparticles can improve drug delivery of histone deacetylase inhibitors for breast cancer therapy without interfering with the mechanism of action of the drug. Keywords: cell cycle, apoptosis, DNA fragmentation, gene expression, epigenetics, MCF-7
format	article
author	Alp E Damkaci F Guven E Tenniswood M
author_facet	Alp E Damkaci F Guven E Tenniswood M
author_sort	Alp E
title	Starch nanoparticles for delivery of the histone deacetylase inhibitor CG-1521 in breast cancer treatment
title_short	Starch nanoparticles for delivery of the histone deacetylase inhibitor CG-1521 in breast cancer treatment
title_full	Starch nanoparticles for delivery of the histone deacetylase inhibitor CG-1521 in breast cancer treatment
title_fullStr	Starch nanoparticles for delivery of the histone deacetylase inhibitor CG-1521 in breast cancer treatment
title_full_unstemmed	Starch nanoparticles for delivery of the histone deacetylase inhibitor CG-1521 in breast cancer treatment
title_sort	starch nanoparticles for delivery of the histone deacetylase inhibitor cg-1521 in breast cancer treatment
publisher	Dove Medical Press
publishDate	2019
url	https://doaj.org/article/0c1ed394cb96489eb89ecd40836a2479
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_version_	1718398525815914496

Starch nanoparticles for delivery of the histone deacetylase inhibitor CG-1521 in breast cancer treatment

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