HEPARIN RELEASE FROM THERMOSENSITIVE POLYMER-COATINGS - IN-VIVO STUDIES

Biomer/poly(N-isopropylacrylamide)/[poly(NiPAAm)] thermosensitive poly mer blends were prepared and their application as heparin-releasing po lymer coatings for the prevention of surface-induced thrombosis was ex amined. The advantage of using poly(NiPAAm)-based coatings as heparin- releasing polymers is based on the unique temperature-dependent swelli ng of these materials. At room temperature, i.e., below the lower crit ical solution temperature (LCST) of poly(NiPAAm), the Biomer/(poly(NiP AAm) coatings are highly swollen. The high swelling enables fast loadi ng of hydrophilic macromolecules (e.g., heparin) into the coating by a solution sorption technique. At a body temperature, i.e., above the L CST of poly(NiPAAm) the coatings are in a deswollen state and the abso rbed macromolecules may be slowly released from a dense coating via a diffusion controlled mechanism. Biomer/poly(NiPAAm) coatings were obta ined by blending and coprecipitation of the two linear polymers, Biome r and (poly(NiPAAm). The structure and water-swelling properties of th e coatings were examined. Significant differences in water swelling at room temperature (RT) and 37 degrees C were observed as a result of t he thermosensitivity of poly(NiPAAm). The surface structure of the coa tings in dry and swollen states at RT and 37 degrees C was examined by scanning electron microscopy. Heparin was loaded into the coatings vi a a solution sorption at room temperature. Kinetic studies of heparin loading demonstrated that maximum loading was obtained within 1 h. The in vitro (37 degrees C) release profiles were characterized by a rapi d initial release due to the squeezing effect of the collapsing polyme r network, followed by a slower release phase controlled by heparin di ffusion through the dense coating. The short-term antithrombogenicity of intravenous polyurethane catheters coated with heparin-releasing Bi omer/poly(NiPAAm) thermosensitive coating was evaluated in a canine an imal model. The results show that the heparin release from Biomer/poly (NiPAAm)-coated surfaces resulted in a significant reduction of thromb us formation on test surfaces in contact with venous blood as compared to control surfaces. (C) 1995 John Wiley and Sons, Inc.