There is a need for the further development of endovascular stents that inhibit stenosis as well as restenosis after angioplasty. There are a number of stents currently in clinical trials and the most effective have been the class of drug-eluting stents. However, there are concerns with the potential medical complications in patients with current drug-eluting stents. Icon Interventional Systems, Inc. has interest in this market and has been developing a coated, metallic stent that releases the biologic chemical, triazolopyrimidine. Our hypothesis is that triazolopyrimidine, can be delivered locally to coronary arteries after angioplasty and by its controlled release, have the ultimate goal of preventing in-stent stenosis and/or restenosis. The specific aims of the proposed project are: (1) to demonstrate that a metal stent could be coated uniformly with varying masses of triazolopyrimidine, followed by a proprietary parylene barrier, providing a mechanism for controlled release; (2) to determine the release kinetics of triazolopyrimidine in vitro by spectrophotometry and HPLC methodologies; (3) to determine in vitro and in vivo biocompatibility and efficacy of triazolopyrimidine and parylene using appropriate cell and animal models. At the end of this Phase I plan, we will have demonstrated that triazolopyrimidine can be coated on a metal stent followed by a uniform coating of parylene, which does not disrupt or delaminate upon expansion, and that a parylene barrier over the triazolopyrimidine coating on the metal stent provides a sustained release of drug. Controlled release of triazolopyrimidine from stents should provide anti-proliferative, anti-migratory and non-toxic effects on smooth muscle cells or endothelial cells in vitro. In vivo biocompatibility tests will show that parylene and triazolopyrimidine are biocompatible. Our intention is to obtain sufficient information to allow us to proceed to Phase II in which further studies to improve upon on the coating procedure and effective drug release to validate the effect in an in vivo model of angioplasty using a porcine model.
