Weill Cornell Medical College, New York, NY, USA.
J Vasc Surg. 2013 May;57(5):1403-14. doi: 10.1016/j.jvs.2012.12.069.
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.
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.
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.
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.
尽管在血管生物学、生物工程和药理学方面取得了重大进展，但血管重建（包括经皮和开放两种方式）的整体疗效仍受到再狭窄的限制。尽管内膜增生的病理生理学很复杂，但已经确定了一些可以预防再狭窄的药物和分子工具。此外，该过程的局灶性使其适用于局部药物给药治疗。本文广泛概述了为预防血管介入后再狭窄而开发的当前和未来的局部药物输送技术。
通过 PubMed 进行了系统的电子文献检索，检索范围包括截至 2012 年 9 月的所有可获取的已发表文章。为了保持时效性，还对相关学会会议上提交的摘要、已归档的专利、临床试验和受美国国立卫生研究院资助的奖项进行了额外的搜索。
局部药物输送的疗效已在冠状动脉循环中得到证实，目前正在使用药物洗脱支架进行临床应用。然而，直到最近，药物洗脱支架在周围血管循环中都没有显示出疗效。对腔内装置的进一步研究导致了基于球囊的技术的发展，最近涉及药物洗脱球囊的试验激增。早期数据令人鼓舞，特别是对于治疗股浅动脉病变，并且最近有几种设备在欧洲获得了 Conformité Européene 标记。研究人员还探索了含有抗再狭窄药物的生物材料的血管周围应用，这种方法对于外科旁路或内膜切除术尤其有用。过去，全身药物输送并不成功；然而，最近已经探索了专门设计用于靶向受损或重建动脉的药物的静脉内输送。我们的综述揭示了许多其他有趣的策略，包括过去 2 年期间针对预防再狭窄的局部药物输送方法发布的超过 65 项新专利。
腔内或开放血管重建后的再狭窄仍然是一个重要的临床问题。在冠状动脉循环中的成功并没有转化为外周动脉的解决方案。然而，我们的文献综述揭示了许多有前途的方法，包括药物洗脱球囊、血管周围药物输送和靶向全身治疗。这些和其他创新表明，未来是光明的，预防外周血管再狭窄的解决方案即将问世。
