Anticoagulant heparin mimetics via RAFT polymerization

Journal Publication ResearchOnline@JCU
Al Nahain, Abdullah;Ignjatovic, Vera;Monagle, Paul;Tsanaktsidis, John;Vamvounis, George;Ferro, Vito
Abstract

Heparin, a sulfated polysaccharide derivedfrom animal sources, is the most commonly used parenteralanticoagulant drug, but it suffers from significant safety andsupply issues. Herein, we describe the preparation of heparinmimetic homo- and copolymers via the reversible addition−fragmentation chain transfer (RAFT) polymerization in waterof commercially available (non-carbohydrate) sulfonated andcarboxylated monomers. The anticoagulant activities of thepolymers were assessed by activated partial thromboplastintime (APTT), thrombin clotting time (TCT), and for the more promising polymers, thrombin generation, antifactor Xa, andantifactor IIa assays. Sulfonated homopolymers studied herein displayed low cytotoxicity and significant anticoagulant activity inAPTT, TCT, and thrombin generation assays. In addition, copolymers of sodium styrenesulfonate and acrylic acid [poly(SSS-co-AA)] displayed unprecedented antifactor IIa activity. This study demonstrates the potential of RAFT polymers as lternativeanticoagulants for biomedical applications.

Journal

Biomacromolecules

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Volume

21

ISBN/ISSN

1526-4602

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Issue

2

Pages Count

13

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Publisher

American Chemical Society

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EISSN

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DOI

10.1021/acs.biomac.9b01688