Control of Heparin Surface Density in Multilayers of Partially Hydrolyzed Poly(2-ethyl-2-oxazoline) by Degree of Hydrolysis

Controlling the surface density of heparin in active anticoagulant coatings is important in applications where an optimum is required. 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 pH5 in 0.5M aqueous NaCl solutions by electrostatic interactions between negatively charged heparin and the positively charged amine groups in hydrolyzed PEOX. Characterization of the multilayers by QCM-D, TBO assay and XPS all show 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, ITC measurements exhibit an exothermic enthalpy below -500 kJ/mol, TBO assay gives a heparin surface density of 1.03 ug/cm2 and atomic % of sulfur as determined by XPS leveled off at ~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.