Local Drug Delivery to Prevent Restenosis

Introduction: Despite significant advances in vascular biology, bioengineering, and pharmacology, restenosis remains a limitation to the overall efficacy of vascular reconstructions, both percutaneous and open. Although the pathophysiology of intimal hyperplasia is complex, a number of drugs and molecular tools have been identified that can prevent restenosis. Moreover, the focal nature of this process lends itself to treatment with local drug administration. This article provides a broad overview of current and future techniques for local drug delivery that have been developed to prevent restenosis after vascular interventions.

Methods: A systematic electronic literature search using PubMed was performed for all accessible published articles through September 2012. In an effort to remain current, additional searches were performed for abstracts presented at relevant societal meetings, filed patents, clinical trials, and funded National Institutes of Health awards.

Results: The efficacy of local drug delivery has been demonstrated in the coronary circulation with the current clinical use of drug-eluting stents. Until recently, however, drug-eluting stents were not found to be efficacious in the peripheral circulation. Further pursuit of intraluminal devices has led to the development of balloon-based technologies, with a recent surge in trials involving drug-eluting balloons. Early data appear encouraging, particularly for treatment of superficial femoral artery lesions, and several devices have recently received the Conformité Européene mark in Europe. Investigators have also explored the periadventitial application of biomaterials containing antirestenotic drugs, an approach that could be particularly useful for surgical bypass or endarterectomy. In the past, systemic drug delivery has been unsuccessful; however, there has been recent exploration of intravenous delivery of drugs designed specifically to target injured or reconstructed arteries. Our review revealed a multitude of additional interesting strategies, including >65 new patents issued during the past 2 years for approaches to local drug delivery focused on preventing restenosis.

Conclusions: Restenosis after intraluminal or open vascular reconstruction remains an important clinical problem. Success in the coronary circulation has not translated into solutions for the peripheral arteries. However, our literature review reveals a number of promising approaches, including drug-eluting balloons, periadventitial drug delivery, and targeted systemic therapies. These and other innovations suggest that the future is bright and that a solution for preventing restenosis in peripheral vessels will soon be at hand.