Stent development and local drug delivery

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Abstract
Stent implantation has become the new standard angioplasty procedure. In-stent re-stenosis remains the major limitation of coronary stenting. Re-stenosis is related to patient-, lesion- and procedure-specific factors. Patient-specific factors can not be influenced to any extent. Procedure-specific factors are affected by implantation technique and stent characteristics. Design and material influence vascular injury and humoral and cellular response. Radiation has been shown to have inhibitory effects on smooth muscle cell growth and neo-intima formation, but in clinical trials the outcome has been hampered by re-stenosis at the edges of the radioactive stent (‘candy wrapper’). New approaches target pharmacological modulation of local vascular biology by local administration of drugs. This allows for drug application at the precise site and time of vessel injury. Systemic release is minimal and this may reduce the risk of toxicity. The drug and the delivery vehicle must fulfil pharmacological, pharmacokinetic and mechanical requirements and the application of eluting degradable matrices seems to be a possible solution. Numerous pharmacological agents with antiproliferative properties are currently under clinical investigation, e.g. actinomycin D, rapamycin or paclitaxel. Another approach is for stents to be made of biodegradable materials as an alternative to metallic stents. Their potential long-term complications, such as in-stent re-stenosis and the inaccessibility of the lesion site for surgical revascularization, needs to be assessed. Current investigational devices and the line of (pre)clinical investigation are discussed in detail. Currently, there is little experimental, and only preliminary clinical, understanding of the acute and long-term effects of drug-eluting or biodegradable stents in coronary arteries. The clinical benefit of these approaches still has to be proven.