Heparin release from thermosensitive polymer coatings: in vivo studies

J Biomed Mater Res. 1995 Jul;29(7):811-21. doi: 10.1002/jbm.820290705.

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acrylic Resins / chemistry*
  • Animals
  • Anticoagulants / administration & dosage
  • Anticoagulants / chemistry*
  • Catheterization
  • Diffusion
  • Dogs
  • Heparin / administration & dosage
  • Heparin / chemistry*
  • Kinetics
  • Microscopy, Electron, Scanning
  • Polyurethanes
  • Solubility
  • Temperature
  • Thrombosis / blood
  • Thrombosis / prevention & control

Substances

  • Acrylic Resins
  • Anticoagulants
  • Polyurethanes
  • poly-N-isopropylacrylamide
  • Heparin