Incorporation of heparin-binding proteins into preformed dextran sulfate-chitosan nanoparticles

Paula Zaman,1 Julia Wang,1 Adam Blau,1 Weiping Wang,2 Tina Li,1 Daniel S Kohane,2 Joseph Loscalzo,1 Ying-Yi Zhang1 1Department of Medicine, Brigham and Women’s Hospital, 2Department of Anesthesiology, Boston Children’s Hospital, Harvard Medical School, Boston, MA, USA Abstract:...

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Autores principales: Zaman P, Wang J, Blau A, Wang W, Li T, Kohane DS, Loscalzo J, Zhang YY
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Publicado: Dove Medical Press 2016
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spelling oai:doaj.org-article:6c2acd9bf99141c4beee071a1351dfbc2021-12-02T03:54:52ZIncorporation of heparin-binding proteins into preformed dextran sulfate-chitosan nanoparticles1178-2013https://doaj.org/article/6c2acd9bf99141c4beee071a1351dfbc2016-11-01T00:00:00Zhttps://www.dovepress.com/incorporation-of-heparin-binding-proteins-into-preformed-dextran-sulf-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Paula Zaman,1 Julia Wang,1 Adam Blau,1 Weiping Wang,2 Tina Li,1 Daniel S Kohane,2 Joseph Loscalzo,1 Ying-Yi Zhang1 1Department of Medicine, Brigham and Women’s Hospital, 2Department of Anesthesiology, Boston Children’s Hospital, Harvard Medical School, Boston, MA, USA Abstract: Incorporation of proteins into dextran sulfate (DS)-chitosan (CS) nanoparticles (DSCS NPs) is commonly performed using entrapment procedures, in which protein molecules are mixed with DS and CS until particle formation occurs. As DS is an analog of heparin, the authors examined whether proteins could be directly incorporated into preformed DSCS NPs through a heparin binding domain-mediated interaction. The authors formulated negatively-charged DSCS NPs, and quantified the amount of charged DS in the outer shell of the particles. The authors then mixed the DSCS NPs with heparin-binding proteins (SDF-1α, VEGF, FGF-2, BMP-2, or lysozyme) to achieve incorporation. Data show that for DSCS NPs containing 100 nmol charged glucose sulfate units in DS, up to ~1.5 nmol of monomeric or ~0.75 nmol of dimeric heparin-binding proteins were incorporated without significantly altering the size or zeta potential of the particles. Incorporation efficiencies of these proteins were 95%–100%. In contrast, serum albumin or serum globulin showed minimal incorporation (8% and 4%, respectively) in 50% physiological saline, despite their large adsorption in water (80% and 92%, respectively). The NP-incorporated SDF-1α and VEGF exhibited full activity and sustained thermal stability. An in vivo aerosolization study showed that NP-incorporated SDF-1α persisted in rat lungs for 72 h (~34% remaining), while free SDF-1α was no longer detectable after 16 h. As many growth factors and cytokines contain heparin-binding sites/domains, incorporation into preformed DSCS NPs could facilitate in vivo applications of these proteins. Keywords: polyelectrolyte complex, polysaccharide, glycan, glycosaminoglycanZaman PWang JBlau AWang WLi TKohane DSLoscalzo JZhang YYDove Medical Pressarticlepolyelectrolyte complexpolysaccharideglycanglycosaminoglycanMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 11, Pp 6149-6159 (2016)
institution DOAJ
collection DOAJ
language EN
topic polyelectrolyte complex
polysaccharide
glycan
glycosaminoglycan
Medicine (General)
R5-920
spellingShingle polyelectrolyte complex
polysaccharide
glycan
glycosaminoglycan
Medicine (General)
R5-920
Zaman P
Wang J
Blau A
Wang W
Li T
Kohane DS
Loscalzo J
Zhang YY
Incorporation of heparin-binding proteins into preformed dextran sulfate-chitosan nanoparticles
description Paula Zaman,1 Julia Wang,1 Adam Blau,1 Weiping Wang,2 Tina Li,1 Daniel S Kohane,2 Joseph Loscalzo,1 Ying-Yi Zhang1 1Department of Medicine, Brigham and Women’s Hospital, 2Department of Anesthesiology, Boston Children’s Hospital, Harvard Medical School, Boston, MA, USA Abstract: Incorporation of proteins into dextran sulfate (DS)-chitosan (CS) nanoparticles (DSCS NPs) is commonly performed using entrapment procedures, in which protein molecules are mixed with DS and CS until particle formation occurs. As DS is an analog of heparin, the authors examined whether proteins could be directly incorporated into preformed DSCS NPs through a heparin binding domain-mediated interaction. The authors formulated negatively-charged DSCS NPs, and quantified the amount of charged DS in the outer shell of the particles. The authors then mixed the DSCS NPs with heparin-binding proteins (SDF-1α, VEGF, FGF-2, BMP-2, or lysozyme) to achieve incorporation. Data show that for DSCS NPs containing 100 nmol charged glucose sulfate units in DS, up to ~1.5 nmol of monomeric or ~0.75 nmol of dimeric heparin-binding proteins were incorporated without significantly altering the size or zeta potential of the particles. Incorporation efficiencies of these proteins were 95%–100%. In contrast, serum albumin or serum globulin showed minimal incorporation (8% and 4%, respectively) in 50% physiological saline, despite their large adsorption in water (80% and 92%, respectively). The NP-incorporated SDF-1α and VEGF exhibited full activity and sustained thermal stability. An in vivo aerosolization study showed that NP-incorporated SDF-1α persisted in rat lungs for 72 h (~34% remaining), while free SDF-1α was no longer detectable after 16 h. As many growth factors and cytokines contain heparin-binding sites/domains, incorporation into preformed DSCS NPs could facilitate in vivo applications of these proteins. Keywords: polyelectrolyte complex, polysaccharide, glycan, glycosaminoglycan
format article
author Zaman P
Wang J
Blau A
Wang W
Li T
Kohane DS
Loscalzo J
Zhang YY
author_facet Zaman P
Wang J
Blau A
Wang W
Li T
Kohane DS
Loscalzo J
Zhang YY
author_sort Zaman P
title Incorporation of heparin-binding proteins into preformed dextran sulfate-chitosan nanoparticles
title_short Incorporation of heparin-binding proteins into preformed dextran sulfate-chitosan nanoparticles
title_full Incorporation of heparin-binding proteins into preformed dextran sulfate-chitosan nanoparticles
title_fullStr Incorporation of heparin-binding proteins into preformed dextran sulfate-chitosan nanoparticles
title_full_unstemmed Incorporation of heparin-binding proteins into preformed dextran sulfate-chitosan nanoparticles
title_sort incorporation of heparin-binding proteins into preformed dextran sulfate-chitosan nanoparticles
publisher Dove Medical Press
publishDate 2016
url https://doaj.org/article/6c2acd9bf99141c4beee071a1351dfbc
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