Synthesis and characterization of polystyrene-poly(ethylene oxide)-heparin block copolymers

A procedure for the preparation of new block copolymers composed of a hydrophobic block of polystyrene, a hydrophilic spacer-block of poly(ethylene oxide) and a bioactive block of heparin was investigated. Polystyrene with one amino group per chain was synthesized by free radical oligomerization of styrene in dimethylformamide, using 2-aminoethanethiol as a chain transfer agent. This amino group was used in the coupling reaction with amino-telechelic poly(ethylene oxide) to produce an AB type diblock copolymer with one amino group per polystyrene (PSt)-poly(ethylene oxide) (PEO) chain. The amino-semitelechelic oligo-styrene was converted into the isocyanate-semitelechelic oligo-styrene using toluene 2,4-diisocyanate and subsequent coupling with H2N-PEO-NH2 afforded AB type block copolymers with terminal amino groups. The coupling of PSt-PEO-NH2 with heparin was performed in a DMF-H2O mixture, first by activating the heparin carboxylic groups with EDC at pH 5.1-5.2 and subsequently reacting the activated carboxylic groups with the amino groups of the PSt-PEO-NH2 at pH 7.5. Depending on the molecular weights of the diblock copolymer used 25-29% w/w heparin was incorporated. These polymers will be further evaluated for their blood-compatibility.