Synthesis and evaluation of heparin immobilized “side-on” to polystyrene microspheres coated with end-group activated polyethylene oxide

Thiol (-SH) groups were introduced into unfractionated heparin by reaction of carboxyl groups in its uronic acid residues with 3,3′dithiobis(propanoic)hydrazide. Thiolated heparin derivatives were then linked to pyridyl disulfide-activated polyethylene oxide-polypropylene oxide-polyethylene oxide triblocks, which had previously been coated onto the surfaces of 1.15 μm polystyrene microspheres. The heparin immobilization reaction was monitored spectrophotometrically as colored pyridine-2-thione was released. In addition, the zeta potentials of uncoated, triblock-coated, and heparin-containing microsphere suspensions were recorded to demonstrate the successful attachment of heparin on the surface. However this “side-on” attachment of heparin to pendant, polyethylene oxide chains did not significantly increase the anticoagulant or anti-Factor Xa activity of microsphere suspensions.