Drug-eluting stents: factors governing local pharmacokinetics.

Stent-based drug delivery system is a revolutionary approach to mitigate the negative affects of balloon angioplasty, improve immune responsiveness and prevent hyperplastic growth of smooth muscle in the restenotic state. Its success is therefore empirically associated with effective delivery of potent therapeutics to the target site at a therapeutic concentration, for a sufficient time, and in a biologically active form. However, local delivery with drug-eluting stents imparts large dynamic concentration gradients across tissues that can be difficult to identify, characterize and control. This review explores the factors such as physiological transport forces, drug physicochemical properties, local biological tissue properties and stent design that governs the local pharmacokinetics within the arterial wall by drug-eluting stent. Rational design and optimization of drug-eluting stents for local delivery thus requires a careful consideration of all these factors.

[1]  E. Edelman,et al.  Specific binding to intracellular proteins determines arterial transport properties for rapamycin and paclitaxel. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[2]  J. Jukema,et al.  Local perivascular delivery of anti-restenotic agents from a drug-eluting poly(ε-caprolactone) stent cuff , 2005 .

[3]  E. Edelman,et al.  Arterial paclitaxel distribution and deposition. , 2000, Circulation research.

[4]  E. Edelman,et al.  Impact of transport and drug properties on the local pharmacology of drug-eluting stents , 2003, International journal of cardiovascular interventions.

[5]  E. Edelman,et al.  Carrier proteins determine local pharmacokinetics and arterial distribution of paclitaxel. , 2001, Journal of pharmaceutical sciences.

[6]  F Litvack,et al.  Localized Arterial Wall Drug Delivery From a Polymer‐Coated Removable Metallic Stent: Kinetics, Distribution, and Bioactivity of Forskolin , 1994, Circulation.

[7]  R. Wilensky,et al.  Effect of atherosclerosis on transmural convection an arterial ultrastructure. Implications for local intravascular drug delivery. , 1997, Arteriosclerosis, thrombosis, and vascular biology.

[8]  E. Edelman,et al.  Dose model for stent-based delivery of a radioactive compound for the treatment of restenosis in coronary arteries. , 2003, Medical physics.

[9]  D R Hose,et al.  A Thermal Analogy for Modelling Drug Elution from Cardiovascular Stents , 2004, Computer methods in biomechanics and biomedical engineering.

[10]  Frank Litvack,et al.  The effect of variable dose and release kinetics on neointimal hyperplasia using a novel paclitaxel-eluting stent platform: the Paclitaxel In-Stent Controlled Elution Study (PISCES). , 2005, Journal of the American College of Cardiology.

[11]  Elazer R Edelman,et al.  Arterial heparin deposition: role of diffusion, convection, and extravascular space. , 1998, American journal of physiology. Heart and circulatory physiology.

[12]  Elazer R Edelman,et al.  Arterial Ultrastructure Influences Transport of Locally Delivered Drugs , 2002, Circulation research.

[13]  A. Gershlick Drug eluting stents in 2005 , 2005, Heart.

[14]  E. Edelman,et al.  Correlation of transarterial transport of various dextrans with their physicochemical properties. , 2000, Biomaterials.

[15]  G. Stone,et al.  Update on drug-eluting coronary stents , 2005, Expert review of cardiovascular therapy.

[16]  A. Tzafriri,et al.  Strut Position, Blood Flow, and Drug Deposition: Implications for Single and Overlapping Drug-Eluting Stents , 2005, Circulation.

[17]  E. Edelman,et al.  Tissue concentration of heparin, not administered dose, correlates with the biological response of injured arteries in vivo. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[18]  E. Edelman,et al.  Drug delivery models transported to a new level , 1998, Nature Biotechnology.

[19]  W. Hunter,et al.  Characterization of perivascular poly(lactic-co-glycolic acid) films containing paclitaxel. , 2004, International journal of pharmaceutics.

[20]  E. Edelman,et al.  Computational simulations of local vascular heparin deposition and distribution. , 1996, The American journal of physiology.

[21]  E. Edelman,et al.  Thrombosis Modulates Arterial Drug Distribution for Drug-Eluting Stents , 2005, Circulation.

[22]  E. Edelman,et al.  Tissue average binding and equilibrium distribution: an example with heparin in arterial tissues. , 1996, Biophysical journal.

[23]  E. Edelman,et al.  Measurement of drug distribution in vascular tissue using quantitative fluorescence microscopy. , 1999, Journal of pharmaceutical sciences.

[24]  I. Iakovou,et al.  New Drug-Eluting Stent Technologies , 2005 .

[25]  Local delivery of paclitaxel as a stent coating , 2005 .

[26]  E. Edelman,et al.  Mechanisms of transmural heparin transport in the rat abdominal aorta after local vascular delivery. , 1995, Circulation research.

[27]  E. Edelman,et al.  Drug clearance and arterial uptake after local perivascular delivery to the rat carotid artery. , 1997, Journal of the American College of Cardiology.

[28]  E. Edelman,et al.  Physiological Transport Forces Govern Drug Distribution for Stent-Based Delivery , 2001, Circulation.

[29]  L. Kalachev,et al.  Numerical Simulation of Local Pharmacokinetics of a Drug after Intravascular Delivery with an Eluting Stent , 2002, Journal of drug targeting.

[30]  Rosaire Mongrain,et al.  Numerical modeling of coronary drug eluting stents. , 2005, Studies in health technology and informatics.