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°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°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°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.

Thermodynamic Behavior of Polyelectrolytes with the Lower Critical Solution Temperature (LCST) Phenomenon

“…Macromolecular systems may be tailor-made to shrink in the desired range of pH and/or temperature if the thermodynamic parameters are accurately known. Unlike most of the polymers previously studied [2,7,141, which are responsive to only one kind of stimulus, the present results are an example of multiple and independent responsiveness that may be required in certain applications [4,8,10,11,151. These are the so-called "intelligent" polymer systems [8,191. …”

Platelet responses and coagulation activation on polylactide and heparin–polycaprolactone‐L‐lactide ‐coated polylactide stent struts

“…Azrin et al have demonstrated that locally delivered heparin may reduce platelet deposition up to 80% after PTA. 35 As the rate of leaching was rapid in our study, the efficacy of heparin may have to be improved (1) by combining at least two species of heparin as biodegradable stent coatings-one with rapid and another with slow release, 36 or (2) by altering the conformation of heparinglycosaminoglycan chains 12,37 to overcome or reduce the need both for systemic heparinization and for antithrombotic medication after angioplasty and stenting.…”

Improved microvessel repair: Laser welding with an anti‐thrombotic solder

“…For anti-thrombotic therapy following microvascular repair, a continuous delivery of drugs at the anastomosis should decrease the risk of thrombosis during the healing process. Gradual release of heparin incorporated into polymer structures has been demonstrated as a method of surface anticoagulation [18].…”