Evaluation of the anticoagulant activity and safety of PMPC–PSSS and PMPC–PVBTAC block copolymers

Abstract

Unfractionated heparin (UFH) remains a widely used anticoagulant; however, its use is associated with several limitations, including an elevated risk of bleeding, the potential for heparin-induced thrombocytopenia, and the necessity for frequent monitoring. Alternative anticoagulants with a lower risk of adverse effects and more predictable pharmacokinetics are currently under investigation. This study evaluates the anticoagulant activity and safety of poly(2-methacryloyloxyethyl phosphorylcholine)-poly(sodium styrenesulfonate) (PMPC₂₀–PSSS_x, x = 83 and 198) anionic block copolymers and poly(2-methacryloyloxyethyl phosphorylcholine)–poly(vinylbenzyl trimethylammonium chloride) (PMPC₂₀–PVBTAC_y, y = 92 and 196) cationic block copolymers. PVBTAC-based cationic block copolymers exhibited stronger in vitro anticoagulant activity in whole blood than PSSS-based anionic block copolymers but caused adverse effects on blood cells. The PMPC₂₀–PSSS₈₃ anionic block copolymer affected the in vitro activity of factors II, V, VIII, IX, X, and XII and exhibited potent anticoagulant effects in a rat model, without significant changes in haemolysis, platelet count, or cardiorespiratory parameters. Due to its high biocompatibility and strong anticoagulant effect, PMPC₂₀–PSSS₈₃ is a promising candidate with notable therapeutic potential in clinical applications.