Heparin release from thermosensitive hydrogels

Thermosensitive hydrogels (TSH) were synthesized and investigated as heparin releasing polymers for the prevention of surface induced thrombosis. TSH were synthesized with N-isopropyl acrylamide (NiPAAm) copolymerized with butyl methacrylate (BMA) (hydrophobic) or acrylic acid (AAc) (hydrophilic) comonomers. The incorporation of hydrophobic and hydrophilic comonomers strongly influences the swelling/shrinking behavior of TSH. Upon deswelling, gels containing the hydrophobic comonomer formed a skin-type layer, which acted as a rate controlling membrane, while the hydrophilic comonomer greatly increased gel swelling, relative to NiPAAm. Equilibrium swelling in isotonic PBS and deswelling kinetics of the synthesized gels were examined at various temperatures. The loading of heparin into the different gels was studied as a function of temperature, solution concentration, and gel composition. The release kinetics of heparin was found to be influenced by gel composition and loading temperature; the release correlated with the gel deswelling kinetics. In the case of Ni-PAAm/BMA gel, the release profile of heparin was affected by temperature dependent properties of the skin-type diffusional barrier formed on the gel surface.