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

Authors Zaman P, Wang J, Blau A, Wang W, Li T, Kohane DS, Loscalzo J, Zhang YY

Received 6 August 2016

Accepted for publication 15 September 2016

Published 18 November 2016 Volume 2016:11 Pages 6149—6159

DOI https://doi.org/10.2147/IJN.S119174

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Thomas Webster


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

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