Strategies for Treating Arterial Restenosis Using Polymeric Controlled Release Implants

Abstract

Coronary artery obstruction is currently being treated with a number of invasive approaches involving catheter based angioplasty procedures. These have included most recently balloon angioplasty combined with expansion of obstructed coronary arteries using balloon expandable stainless steel stents. However, angioplasty itself, especially with stenting, leads to an accelerated reobstruction process, known as restenosis. Research reported in this paper has investigated an approach to preventing restenosis using controlled release drug-polymer implants for local inhibition of the pathophysiologic events of restenosis. Model therapeutic compounds were chosen including aspirin, as an antiplatelet agent, hirulog, as an antithrombin, and colchicine as an antiproliferative. Controlled release polymer matrices were successfully formulated and characterized. Retention of anticoagulant activity for the peptide, hirulog, was demonstrated in vitro. These polymers are suitable for investigations in periadventitial implants and animal models of restenosis. Eventually, controlled release strategies for preventing restenosis will involve integrating of ideal agents including gene therapy, with stents and related devices in order to develop a drug delivery systems approach.