The Taxus drug-eluting stent: a new paradigm in controlled drug delivery.

The advent of drug-eluting stents (DES) has provided the medical community with a technology that is transforming the treatment of coronary artery disease. As the newest treatment modality available to the interventional cardiologist, drug-eluting stents have not only significantly reduced the risk of restenosis, but they are also allowing the interventionalists to treat more complex lesions in patients that would otherwise require more invasive bypass surgery. Development of these drug-device combination products has presented considerable challenges to the device industry because it involves a multi-disciplinary approach that combines conventional device design and manufacturing with the principles of controlled local drug delivery. This review article provides an in-depth discussion of the key elements of drug-eluting stents, focusing on the TAXUS paclitaxel-eluting stent as an example of this new class of product. Specific sections will review the drug and polymer matrix components, formulation development and evaluation, pre-clinical studies and clinical trial results.

[1]  M. Helmus,et al.  Physical characterization of controlled release of paclitaxel from the TAXUS Express2 drug-eluting stent. , 2004, Journal of biomedical materials research. Part A.

[2]  P. Schiff,et al.  Promotion of microtubule assembly in vitro by taxol , 1979, Nature.

[3]  S. Silber,et al.  Randomized Study to Assess the Effectiveness of Slow- and Moderate-Release Polymer-Based Paclitaxel-Eluting Stents for Coronary Artery Lesions , 2003, Circulation.

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

[5]  T. Higuchi,et al.  Rate of release of medicaments from ointment bases containing drugs in suspension. , 1961, Journal of pharmaceutical sciences.

[6]  B. Abella,et al.  Paclitaxel Stent Coating Inhibits Neointimal Hyperplasia at 4 Weeks in a Porcine Model of Coronary Restenosis , 2001, Circulation.

[7]  D. Faxon,et al.  Remodeling of the coronary artery after vascular injury. , 1997, Progress in cardiovascular diseases.

[8]  Stephen R Byrn,et al.  Solid-state analysis of the active pharmaceutical ingredient in drug products. , 2003, Drug discovery today.

[9]  V. Fuster,et al.  Atherosclerotic Vascular Disease Conference: Writing Group III: pathophysiology. , 2004, Circulation.

[10]  Gregg W Stone,et al.  One-Year Clinical Results With the Slow-Release, Polymer-Based, Paclitaxel-Eluting TAXUS Stent: The TAXUS-IV Trial , 2004, Circulation.

[11]  J. Beutler,et al.  1H- and 13C-nmr assignments for taxol, 7-epi-taxol, and cephalomannine. , 1992, Journal of natural products.

[12]  T. Fojo,et al.  Paclitaxel (Taxol(R)) inhibits motility of paclitaxel-resistant human ovarian carcinoma cells. , 1996, Clinical cancer research : an official journal of the American Association for Cancer Research.

[13]  B. McManus,et al.  Complete inhibition of intimal hyperplasia by perivascular delivery of paclitaxel in balloon-injured rat carotid arteries. , 2001, Journal of vascular and interventional radiology : JVIR.

[14]  S. Balasubramanian,et al.  Pharmaceutical and physical properties of paclitaxel (Taxol) complexes with cyclodextrins. , 1995, Journal of pharmaceutical sciences.

[15]  Jeffrey W Moses,et al.  Sirolimus-eluting stents versus standard stents in patients with stenosis in a native coronary artery. , 2003, The New England journal of medicine.

[16]  Elazer R. Edelman,et al.  Drug-Eluting Stents in Preclinical Studies: Recommended Evaluation From a Consensus Group , 2002, Circulation.

[17]  Mary E. Russell,et al.  Comparison of a polymer-based paclitaxel-eluting stent with a bare metal stent in patients with complex coronary artery disease: a randomized controlled trial. , 2005 .

[18]  D. Timmons,et al.  High-performance liquid chromatographic assay of taxol. , 1992, Analytical chemistry.

[19]  A. Küttner,et al.  Paclitaxel inhibits arterial smooth muscle cell proliferation and migration in vitro and in vivo using local drug delivery. , 1997, Circulation.

[20]  J. Popma,et al.  Clinical Efficacy of Polymer-Based Paclitaxel-Eluting Stents in the Treatment of Complex, Long Coronary Artery Lesions From a Multicenter, Randomized Trial: Support for the Use of Drug-Eluting Stents in Contemporary Clinical Practice , 2005, Circulation.

[21]  S. Balasubramanian,et al.  Noncovalent dimerization of paclitaxel in solution: evidence from electrospray ionization mass spectrometry. , 2002, Journal of pharmaceutical sciences.

[22]  A. Küttner,et al.  Inhibition of smooth muscle cell proliferation after local drug delivery of the antimitotic drug paclitaxel using a porous balloon catheter , 2001, Basic Research in Cardiology.

[23]  D. Bugay.  Characterization of the solid-state: spectroscopic techniques. , 2001, Advanced drug delivery reviews.

[24]  G. Ferns,et al.  The mechanisms of coronary restenosis: insights from experimental models , 2000, International journal of experimental pathology.

[25]  P. Libby,et al.  The molecular bases of restenosis. , 1997, Progress in cardiovascular diseases.

[26]  Kinam Park,et al.  Hydrotropic agents for study of in vitro paclitaxel release from polymeric micelles. , 2004, Journal of controlled release : official journal of the Controlled Release Society.

[27]  S. W. Kim,et al.  Regulation of smooth muscle cell proliferation using paclitaxel-loaded poly(ethylene oxide)-poly(lactide/glycolide) nanospheres. , 1998, Journal of biomedical materials research.

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

[29]  J. Alderfer,et al.  Solvent- and concentration-dependent molecular interactions of taxol (Paclitaxel). , 1994, Journal of pharmaceutical sciences.

[30]  Mary E. Russell,et al.  TAXUS I: Six- and Twelve-Month Results From a Randomized, Double-Blind Trial on a Slow-Release Paclitaxel-Eluting Stent for De Novo Coronary Lesions , 2003, Circulation.

[31]  W L Hunter,et al.  Solid-state characterization of paclitaxel. , 1997, Journal of pharmaceutical sciences.

[32]  C. Goodman.  United States Pharmacopeial Convention , 1988 .

[33]  E. Edelman,et al.  Neointimal thickening after stent delivery of paclitaxel: change in composition and arrest of growth over six months. , 2000, Journal of the American College of Cardiology.

[34]  Michael L. Shuler,et al.  Taxol®: science and applications. , 1995 .

[35]  Leon Shargel,et al.  Applied biopharmaceutics and pharmacokinetics , 1980 .

[36]  David E. Bugay,et al.  Physical Characterization of Pharmaceutical Solids , 1995, Pharmaceutical Research.

[37]  Levon M Khachigian,et al.  Coronary In-stent Restenosis: Current Status and Future Strategies , 2022 .

[38]  R. Donehower,et al.  Drug therapy : paclitaxel (Taxol) , 1995 .

[39]  E. Topol,et al.  Frontiers in interventional cardiology. , 1998, Circulation.

[40]  G. Viale,et al.  The microtubule-affecting drug paclitaxel has antiangiogenic activity. , 1996, Clinical cancer research : an official journal of the American Association for Cancer Research.

[41]  C. Cañizares,et al.  The effects of taxol, a potent platelet antiaggregant, may be due to its microtubular stabilization activity. , 1997, Platelets.

[42]  P. Serruys,et al.  A randomized comparison of a sirolimus-eluting stent with a standard stent for coronary revascularization. , 2002, The New England journal of medicine.

[43]  Gregg W Stone,et al.  A polymer-based, paclitaxel-eluting stent in patients with coronary artery disease. , 2004, The New England journal of medicine.

[44]  Muzaffer Degertekin,et al.  TAXUS III Trial: In-Stent Restenosis Treated With Stent-Based Delivery of Paclitaxel Incorporated in a Slow-Release Polymer Formulation , 2003, Circulation.

[45]  Wolfgang Schöber,et al.  The Effects of Paclitaxel on the Three Phases of Restenosis: Smooth Muscle Cell Proliferation, Migration, and Matrix Formation: An In Vitro Study , 2004, Investigative radiology.

[46]  J. Puskas,et al.  Polyisobutylene-Based Thermoplastic Elastomers: A Review , 1996 .

[47]  S. Byrn,et al.  Chemical reactivity in solid-state pharmaceuticals: formulation implications. , 2001, Advanced drug delivery reviews.

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

[49]  Gregg W Stone,et al.  Comparison of a polymer-based paclitaxel-eluting stent with a bare metal stent in patients with complex coronary artery disease: a randomized controlled trial. , 2005, JAMA.

[50]  D. Song,et al.  Binding of taxol to plastic and glass containers and protein under in vitro conditions. , 1996, Journal of pharmaceutical sciences.

[51]  M. Koci,et al.  Interleukin-12 overcomes paclitaxel-mediated suppression of T-cell proliferation. , 1998, Immunopharmacology and immunotoxicology.

[52]  Jeong Hun Lee,et al.  Preparation and Characterization of Solvent Induced Dihydrated, Anhydrous, and Amorphous Paclitaxel , 2001 .

[53]  M. Helmus,et al.  Styrenic block copolymers for biomaterial and drug delivery applications. , 2005, Acta biomaterialia.

[54]  T. Fojo,et al.  Low concentrations of paclitaxel induce cell type-dependent p53, p21 and G1/G2 arrest instead of mitotic arrest: molecular determinants of paclitaxel-induced cytotoxicity , 2001, Oncogene.

[55]  E. Lakatta,et al.  Taxol inhibits neointimal smooth muscle cell accumulation after angioplasty in the rat. , 1995, The Journal of clinical investigation.

[56]  Joseph P. Remington,et al.  Remington's pharmaceutical sciences , 2016 .

[57]  T. Cruz,et al.  Inhibition of activator protein 1 activity by paclitaxel suppresses interleukin-1-induced collagenase and stromelysin expression by bovine chondrocytes. , 1998, Arthritis and rheumatism.

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

[59]  E. Geissler,et al.  THE ANTINEOPLASTIC DRUG PACLITAXEL HAS IMMUNOSUPPRESSIVE PROPERTIES THAT CAN EFFECTIVELY PROMOTE ALLOGRAFT SURVIVAL IN A RAT HEART TRANSPLANT MODEL1 , 2002, Transplantation.

[60]  E. Grulke,et al.  Glass Transition Temperatures of Polymers , 1999 .

[61]  D. M. L. Buellesfeld,et al.  Long-term evaluation of paclitaxel-coated stents for treatment of native coronary lesions , 2003, Zeitschrift für Kardiologie.

[62]  T. Higuchi.  MECHANISM OF SUSTAINED-ACTION MEDICATION. THEORETICAL ANALYSIS OF RATE OF RELEASE OF SOLID DRUGS DISPERSED IN SOLID MATRICES. , 1963, Journal of pharmaceutical sciences.

[63]  Z. Darżynkiewicz,et al.  Paclitaxel Induces Primary and Postmitotic G1 Arrest in Human Arterial Smooth Muscle Cells , 2004, Cell cycle.

[64]  J. Henkin,et al.  Paclitaxel at ultra low concentrations inhibits angiogenesis without affecting cellular microtubule assembly , 2003, Anti-cancer drugs.

[65]  M. Dake,et al.  Inhibition of vascular endothelial growth factor-mediated neointima progression with angiostatin or paclitaxel. , 2002, Journal of vascular and interventional radiology : JVIR.