Local drug delivery via a coronary stent with programmable release pharmacokinetics

Background-Fixed drug release kinetics and vessel wall partitioning may limit the effectiveness of drug-eluting stents. We report preliminary experience using a new coronary stent with programmable pharmacokinetics. Methods and Results-A newly designed metallic stent contains honeycombed strut elements with inlaid stacked layers of drug and polymer. In vitro studies evaluated recipes for loading paclitaxel to establish the parameters for controlling drug release. Manipulation of the layers of biodegradable polymer and drug allowed varying of the initial 24-hour burst release of paclitaxel from 69% to 8.6% (P<0.0001). Late release of drug could be adjusted dependently or independently of early burst release. A biphasic release profile was created by the addition of blank layers of polymer within the stack. In the 30-day porcine coronary model (n=17 pigs), there was a 70% reduction in late loss (0.3+/-0.5 versus 1.0+/-0.5 mm, P=0.04), a 28% increase in luminal volume (132+/-12 versus 103+/-21 mm 3, P=0.02), and a 50% decrease in histological neointimal area (2.0+/-0.5 versus 4.0+/-1.6 mm 2; P<0.001) compared with bare metal controls. Temporal and regional variations in vascular healing were seen histologically. Conclusions-Layered polymer/drug inlay stent technology permits flexible and controllable pharmacokinetic profiles. Programmable, complex chemotherapy using this approach may be feasible for the treatment of cardiovascular disease.