title: Heparin release from thermosensitive polymer coatings: in vivo studies.
abstract: Biomer/poly(N-isopropylacrylamide)/[poly(NiPAAm)] thermosensitive polymer blends were prepared and their application as heparin-releasing polymer coatings for the prevention of surface-induced thrombosis was examined. The advantage of using poly (NiPAAm)-based coatings as heparin-releasing polymers is based on the unique temperature-dependent swelling of these materials. At room temperature, i.e., below the lower critical solution temperature (LCST) of poly (NiPAAm), the Biomer/(poly(NiPAAm) coatings are highly swollen. The high swelling enables fast loading of hydrophilic macromolecules (e.g., heparin) into the coating by a solution sorption technique. At a body temperature, i.e., above the LCST of poly (NiPAAm) the coatings are in a deswollen state and the absorbed macromolecules may be slowly released from a dense coating via a diffusion controlled mechanism. Biomer/poly(NiPAAm) coatings were obtained by blending and coprecipitation of the two linear polymers, Biomer and (poly(NiPAAm). The structure and water-swelling properties of the coatings were examined. Significant differences in water swelling at room temperature (RT) and 37 degrees C were observed as a result of the thermosensitivity of poly (NiPAAm). The surface structure of the coatings in dry and swollen states at RT and 37 degrees C was examined by scanning electron microscopy. Heparin was loaded into the coatings via 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 rapid initial release due to the squeezing effect of the collapsing polymer network, followed by a slower release phase controlled by heparin diffusion through the dense coating. The short-term antithrombogenicity of intravenous polyurethane catheters coated with heparin-releasing Biomer/poly(NiPAAm) thermosensitive coating was evaluated in a canine animal model. The results show that the heparin release from Biomer/poly(NiPAAm)-coated surfaces resulted in a significant reduction of thrombus formation on test surfaces in contact with venous blood as compared to control surfaces.
authors.affiliation: Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City 84108, USA.
authors.forename: A
authors.initials: A
authors.lastname: Gutowska
authors.forename: Y H
authors.initials: YH
authors.lastname: Bae
authors.forename: H
authors.initials: H
authors.lastname: Jacobs
authors.forename: F
authors.initials: F
authors.lastname: Mohammad
authors.forename: D
authors.initials: D
authors.lastname: Mix
authors.forename: J
authors.initials: J
authors.lastname: Feijen
authors.forename: S W
authors.initials: SW
authors.lastname: Kim
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry*; D000818:Animals; D000925:Anticoagulants / Q000008:administration & dosage / Q000737:chemistry*; D002404:Catheterization; D004058:Diffusion; D004285:Dogs; D006493:Heparin / Q000008:administration & dosage / Q000737:chemistry*; D007700:Kinetics; D008855:Microscopy, Electron, Scanning; D011140:Polyurethanes; D012995:Solubility; D013696:Temperature; D013927:Thrombosis / Q000097:blood / Q000517:prevention & control
chemical_list: D000180:Acrylic Resins; D000925:Anticoagulants; D011140:Polyurethanes; C052970:poly-N-isopropylacrylamide; D006493:Heparin