Control of heparin surface density in multilayers of partially hydrolyzed poly(2-ethyl-2-oxazoline) by degree of hydrolysis

Abstract

Controlling the surface density of heparin in active coatings is important in providing anticoagulation while preventing bleeding. An approach based on tuning the degree of hydrolysis of poly(2-ethyl-2-oxazoline) (PEOX) is presented to control the surface density of heparin in layer-by-layer (LbL) assembled films. Multilayers are prepared at pH 5 in 0.5 M aqueous NaCl solutions by electrostatic interactions between negatively charged heparin and the positively charged amine groups in hydrolyzed PEOX. Characterization of the multilayers by quartz crystal microbalance with dissipation (QCM-D), toluidine blue (TBO) assay and X-ray Photoelectron Spectroscopy (XPS) all shows that the amount of heparin deposited increases with the degree of hydrolysis. While non-hydrolyzed PEOX/heparin multilayers do not grow, the average deposited mass per area per bilayer as determined by QCM-D measurements increases with the degree of hydrolysis. At 50% hydrolysis, TBO assay gives a heparin surface density of 1.03 mu g/cm(2) and atomic % of sulfur as determined by XPS leveled off at similar to 14%. These results show the potential of acidic hydrolysis of PEOX combined with LbL assembly of heparin as a reproducible method for controlling the surface density of heparin in anticoagulant coatings.