Abstract
Di- and triblock copolymers with low dispersity of molecular weight were synthesized using radical addition-fragmentation chain transfer polymerization. The copolymers contained anionic poly(sodium 2-acrylamido-2-methylpropanesulfonate) (PAMPS) block as an anticoagulant component. The block added to lower the toxicity was either poly(ethylene glycol) (PEG) or poly(2-(methacryloyloxy)ethyl phosphorylcholine) (PMPC). The polymers prolonged clotting times both in vitro and in vivo. The influence of the polymer architecture and composition on the efficacy of anticoagulation and safety parameters was evaluated. The polymer with the optimal safety/efficacy profile was PEG47- b-PAMPS108, i.e., a block copolymer with the degrees of polymerization of PEG and PAMPS blocks equal to 47 and 108, respectively. The anticoagulant action of copolymers is probably mediated by antithrombin, but it differs from that of unfractionated heparin. PEG47- b-PAMPS108 also inhibited platelet aggregation in vitro and increased the prostacyclin production but had no antiplatelet properties in vivo. PEG47- b-PAMPS108 anticoagulant activity can be efficiently reversed with a copolymer of PEG and poly((3-(methacryloylamino)propyl)trimethylammonium chloride) (PMAPTAC) (PEG41- b-PMAPTAC53, HBC), which may be attributed to the formation of polyelectrolyte complexes with PEG shells without anticoagulant properties.
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