Local vascular toxicokinetics of stent-based drug delivery

One of the major limitations of balloon angioplasty is early restenosis as a result of elastic recoil leading to vessel occlusion. The constrictive (negative) remodeling of the blood vessel is overcome by implanting a balloon expandible metal stent to dilate the artery and thereby prevent elastic recoil. However, bare metal stent implants cause mechanical injury to the intima and release of inflammatory mediators which then initiates formation of neointimal layer leading to restenosis. In-stent restenosis is histologically distinct from restenosis following balloon angioplasty, in which in-stent restenosis is accompanied by increased smooth muscle proliferation, migration, extracellular matrix and collagen synthesis leading to neointimal hyperplasia. To overcome neointimal hyperplasia, stents have been coated with pharmacological agents that inhibit smooth muscle cell proliferation and migration. The drug and polymer combination coated onto stent device is an efficient form of drug delivery system which can provide high concentrations of drug in the tissues over an extended period of time to achieve antiproliferative therapeutic effect. The permanent stent implants pose the risk of a continuous interaction between the non-biodegradable polymer coating and intimal surface leading to physical irritation, endothelial dysfunction, hypersensitivity reactions, delayed healing and excess risk of late stent thrombosis. This review highlights the relationship between local drug delivery using the stent platform, release kinetics and local vascular toxicity.