Local drug delivery to prevent restenosis

Abstract

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/or molecular tools have been identified that can prevent restenosis. Moreover, the focal nature of this process lends itself to treatment with local drug administration. In this article we provide a broad overview of current and future techniques for local drug delivery that have been developed to prevent restenosis following vascular intervention. 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 NIH awards. Results The efficacy of local drug delivery has been demonstrated in the coronary circulation with the current clinical use of drug-eluting stents (DES). Until recently, however, DES 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 appears encouraging, particularly for treatment of lesions in the superficial femoral artery, with several devices having recently received the CE mark in Europe. Investigators have also explored periadventitial application of biomaterials containing anti-restenotic 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 more than 65 new patents issued over the past two years for approaches to local drug delivery focused on preventing restenosis. Conclusion Restenosis following 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 review of the literature reveals a number of promising approaches including drug-eluting balloons, periadventitial drug delivery as well as targeted systemic therapies. These innovations as well as others suggest that the future is bright and a solution for preventing restenosis in peripheral vessels will soon be at hand.

Enhanced Autophagy by Everolimus Contributes to the Antirestenotic Mechanisms in Vascular Smooth Muscle Cells

“…Restenosis remains the major drawback and limits the efficacy of angioplasty for arterial occlusive diseases [1]. The proliferation of vascular smooth muscle cells (VSMCs) contributes to intimal hyperplasia, which is a critical event in the development of restenosis [2].…”

“…However, systemic drug therapy has shown diminished efficacy, narrow therapeutic ranges and poor tolerance [3]. Consequently, intraluminal drug delivery devices, particularly drug-eluting stents (DESs), are being used to prevent restenosis as they slowly and locally release drugs to block cell proliferation [1]. Paclitaxel and sirolimus are the most widely used drugs in DESs [4].…”

Gene therapy for in-stent restenosis: Targets and delivery system

“…First, most catheters require prolonged total occlusion of the target vessel for effective vector delivery, which may increase the risk for myocardial ischemia. Second, there is lack of efficiency in site-specific gene delivery, although current vector delivery systems have focused on modified balloon catheters that can trap a fluid within a short segment of vasculature (84). Finally, the delivered viral or nonviral vectors inevitably disperse from side branches of the coronary vasculature, which carries the potential risk for distal spread.…”

Novel Therapies for Hemodialysis Vascular Access Dysfunction

“…Polymer or metallic alloy bioresorbable stents provide a temporary support for the vessel wall but degrade over time, mitigating such factors. In a clinical trial of single de novo coronary lesions treated with an everolimuseluting bioresorbable polymer stent (48), the stents were shown to be safe; no restenoses or thromboses were reported, and the stented arteries were observed to retain vasomotor responses (49). Use of biodegradable stents for hemodialysis vascular access has not been reported.…”