Anticoagulant heparin mimetics via RAFT polymerization

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.

Biomacromolecules

Biomacromolecules

21

1526-4602

N/A

2

13