Published Online
on January 13, 2003

A more recent version of this article appeared on February 11, 2003

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Submitted on August 8, 2002
Revised on October 18, 2002
Accepted on October 20, 2002

Local Drug Delivery via a Coronary Stent With Programmable Release Pharmacokinetics

Ariel Finkelstein MD, Dougal McClean MB, ChB, MD, Saibal Kar MD, Kaname Takizawa MD, Kiron Varghese MD, Namjin Baek PhD, Kinam Park PhD, Michael C. Fishbein MD, Raj Makkar MD, Frank Litvack MD, and Neal L. Eigler MD^*

From the Division of Cardiology, Cedars-Sinai Medical Center and Department of Pathology at UCLA School of Medicine (M.C.F.), Los Angeles, Calif, and Purdue University (N.B., K.P.), West Lafayette, Ind.

^* To whom correspondence should be addressed. E-mail: ib1surfdoc{at}aol.com.

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 mm³, P=0.02), and a 50% decrease in histological neointimal area (2.0±0.5 versus 4.0±1.6 mm²; 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.

Key words: pharmacokinetics • stents • angioplasty • restenosis

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