Pulsatile local delivery of thrombolytic and antithrombotic agents using poly( N-isopropylacrylamide-co-methacrylic acid) hydrogels

Hydrogels of poly(N-isopropylacrylamide-co-methacrylic acid) were synthesized and investigated as pHand temperature-triggered delivery devices for antithrombotic agents. For hydrogels containing greater than 75 tool% N1PAAm, the pH and temperature sensitivity both influenced the overall swelling behavior of the networks. Streptokinase and heparin were loaded into these hydrogels and their release characteristics were determined under pulsatile conditions. The hydrogels synthesized in this study were capable of pulsatile streptokinase release, with at least one order of magnitude difference in release rates between the swollen and collapsed hydrogel states. However, the much smaller heparin molecule diffused equally rapidly in the collapsed and swollen polymer states.