Division of Cardiology, University of Missouri, One Hospital Drive, Columbia, MO, USA.
Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2012 Jan-Feb;4(1):82-95. doi: 10.1002/wnan.154. Epub 2011 Jul 11.
High-grade atherosclerotic stenoses are reduced to zero or minimal residual stenosis grades by a single or a series of balloon angioplasties. Currently, stents are implanted to prevent immediate vascular recoil and elution of an antimitotic drug from the stent struts minimizes restenosis. An unwanted side-effect of this drug elution is delayed re-endothelialization which requires treatment with two anti-platelet drugs, in many cases for a minimum of 1 year to prevent acute in-stent thrombosis. Advances in stent design and drug elution technology, now in its fourth generation, have not abated this issue. Nanotechnology-based local drug delivery has the potential to achieve restenosis prevention while not impeding endothelial healing. Molecularly targeted drugs can be aimed to specifically bind to epitopes in the injured media and adventitia. Thus, endothelial healing may progress unhindered. To prevent restenosis, this technology may be used with bare metal or biodegradable stents. In this article novel nanoparticulate agents will be compared regarding their potential to deliver drugs to molecular targets within the vascular wall. Potential molecular targets, targeting mechanisms, drug-delivery propensities, and biocompatibility will be reviewed.
通过单次或多次球囊血管成形术,可将高级动脉粥样硬化性狭窄减少至零或最小残留狭窄程度。目前,支架的植入是为了防止血管即时回缩,并使支架梁中的抗有丝分裂药物洗脱,从而将再狭窄最小化。这种药物洗脱的一个不良副作用是内皮延迟再内皮化,这需要使用两种抗血小板药物治疗,在许多情况下至少需要 1 年,以防止急性支架内血栓形成。支架设计和药物洗脱技术的进步,现已进入第四代,但仍未能解决这个问题。基于纳米技术的局部药物输送有可能在不阻碍内皮愈合的情况下预防再狭窄。靶向药物可以针对损伤的中膜和外膜中的特定表位。因此,内皮愈合可能不受阻碍。为了预防再狭窄,这项技术可与裸金属或可生物降解支架一起使用。本文将比较新型的纳米颗粒制剂在将药物递送至血管壁内的分子靶标方面的潜力。将对潜在的分子靶标、靶向机制、药物输送倾向和生物相容性进行综述。