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In vitro chelating, cytotoxicity, and blood compatibility of degradable poly(ethylene glycol)-based macromolecular iron chelators

Paper ID Volume ID Publish Year Pages File Format Full-Text
10839 703 2009 11 PDF Available
Title
In vitro chelating, cytotoxicity, and blood compatibility of degradable poly(ethylene glycol)-based macromolecular iron chelators
Abstract

Desferrioxamine (DFO) is used to treat an excess accumulation of iron in the body and is currently the most commonly used iron chelator for the treatment of ‘iron overload’ disorder. However, the disadvantages of DFO surround its high toxicity and very short plasma half-life. Here, the detailed in vitro evaluation of a novel class of high molecular weight iron chelators based on DFO and polyethylene glycol methacrylate is reported. Reversible addition fragment chain transfer (RAFT) copolymerization afforded polymer conjugates (P-DFO) with well-controlled molecular weight (27–127 kDa) and substitution of DFO (5–26 units per chain) along the copolymer. Human umbilical vein endothelial cell (HUVEC) based cell viability assays showed that the cytotoxicity of P-DFO decreased more than 100-fold at identical concentrations of DFO. The hemocompatibilities of various P-DFO samples were determined by measuring prothrombin time (PT), activated partial thromboplastin time (APTT), thrombelastograph parameters (TEG), complement activation, platelet activation, and red blood cell aggregation. Furthermore, the iron binding properties and chelating efficiency of P-DFO were compared to DFO by measuring the spectral properties upon binding to iron(III), while the prevention of iron(III) mediated oxidation of hemoglobin was also determined. Degradation of the P-DFO conjugates via cleavable ester linkages between the polymer backbone and the PEG side chains was evaluated using gel permeation chromatography (GPC) and NMR. Since the chelating ability of DFO remains intact after conjugation to the copolymer backbone, these macromolecular, blood compatible and degradable conjugates are promising candidates as long circulating, non-toxic iron chelators.

Keywords
Iron chelation therapy; Desferrioxamine; Poly(ethylene glycol) (PEG); RAFT polymerization; Blood compatibility; Macromolecular therapeutics
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In vitro chelating, cytotoxicity, and blood compatibility of degradable poly(ethylene glycol)-based macromolecular iron chelators
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 30, Issue 4, February 2009, Pages 638–648
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us