Anticoagulant Heparin Mimetics via RAFT Polymerization

Area of Science:

• Biomaterials Science
• Polymer Chemistry
• Pharmacology

Background:

• Heparin, a widely used anticoagulant, faces safety and supply challenges due to its animal origin.
• Development of synthetic anticoagulants is crucial for reliable and safe therapeutic options.

Purpose of the Study:

• To synthesize heparin mimetic homo- and copolymers using reversible addition-fragmentation chain transfer (RAFT) polymerization.
• To evaluate the anticoagulant properties and cytotoxicity of these novel synthetic polymers.

Main Methods:

• Synthesis of sulfonated and carboxylated polymers via RAFT polymerization in water.
• Assessment of anticoagulant activity using activated partial thromboplastin time (APTT), thrombin clotting time (TCT), thrombin generation, antifactor Xa, and antifactor IIa assays.
• Evaluation of polymer cytotoxicity.

Main Results:

• Sulfonated homopolymers exhibited low cytotoxicity and potent anticoagulant effects in APTT, TCT, and thrombin generation assays.
• Copolymers of sodium styrenesulfonate and acrylic acid demonstrated significant antifactor IIa activity.
• The developed polymers show promise as effective anticoagulants.

Conclusions:

• RAFT polymerization offers a viable route to synthesize heparin mimetics.
• These synthetic polymers represent a potential alternative to animal-derived heparin for anticoagulant therapy.
• Further development could lead to safer and more accessible anticoagulant drugs.