Local drug delivery in restenosis injury: Thermoresponsive co-polymers as potential drug delivery systems

The success of percutaneous transluminal coronary angioplasty in treatment of acute coronary syndromes has been compromised by the incidence of restenosis. The physical insult of balloon insertion can damage or remove the endothelial monolayer, thereby generating a prothrombotic surface. The resulting inappropriate response to injury can also lead to penetration of inflammatory cells, conversion of the underlying media to a synthetic phenotype, deposition of extracellular matrix, constrictive remodeling, and neointimal hyperplasia. While stent implantation at the time of balloon insertion has offset some of these events, inflammatory responses to the implanted biomaterial (stent) and intimal hyperplasia are still prominent features of the procedure, leading in 20-30% of cases to in-stent restenosis within a year. Systemic delivery of drugs designed to offset in-stent restenosis injury has been largely unsuccessful, which has led to the development of strategies for coating stents with drugs for local delivery. Drug-eluting stents constitute an innovative means of further reducing the incidence of restenosis injury and clinical trials have shown encouraging results. This review focuses on properties of a class of environment-sensitive hydrogels, the N-isopropylacrylamide-based thermoresponsive co-polymers, on their potential roles as stent coatings, on their demonstrated ability to incorporate and release drugs that modify vascular endothelial and smooth muscle cell functions, and on issues that still await clarification, prior to their adoption in a clinical setting.