Drug Delivery by Angiographic Contrast Media: Inhibition of Restenosis

Abstract

Angioplasty without and with stent implantation is an established minimally invasive procedure for treating localized stenosis in a variety of blood vessels. A high acute success rate is reduced by restenosis within the following months mainly due to neointimal hyperplasia induced by the unavoidable injury of the vessel wall. Rapamycinand paclitaxel-eluting stents significantly delay or reduce restenosis in animal experiments and patients [1, 2]. According to current concepts sustained release of efficacious antiproliferative drugs is required to achieve this effect [3]. Rapamycin and paclitaxel are highly lipophilic and poorly water-soluble. These agents may rapidly enter the local vessel wall when dissolved in contrast media (CM) and administered for selective angiography during interventional procedures. This may be sufficient to prevent restenosis if high enough local concentrations are reached and suppression of cell proliferation is maintained for the critical period of time following injury. Results reported at the CMR 2001 [4] indicated the efficacy of this approach. Additional studies were designed to investigate the dose dependency of the effects of paclitaxel added to CM in the porcine coronary stent model and to measure local drug concentrations.