Stents as a platform for drug delivery

Introduction: Drug delivery stents have proved their efficacy at preventing coronary restenosis and their potential in treating the occlusion or stricture of other body passageways, such as peripheral vessels and alimentary canals. The drug delivery systems on such stent platforms contribute to this improved therapeutic efficacy by providing improved drug delivery performance, along with reduced concerns encountered by current stents (e.g., in-stent restenosis, late thrombosis and delayed healing). Areas covered: A wide variety of drug delivery stents (metallic drug-eluting stents, absorbable drug-eluting stents, and polymer-free drug-eluting stents for coronary and other applications) that are commercially available or under investigation are collected and summarized in this review, with emphasis on their drug delivery aspects. This review also gives insights into the progression of stent-based drug delivery strategies for the prevention of stent-related problems, or the treatment of local diseases. In addition, a critical analysis of the advantages and challenges of such strategies is provided. Expert opinion: With an in-depth understanding of drug properties, tissue/organ biology and disease conditions, stent drug delivery systems can be improved further, to endow the stents with better efficacy and safety, along with lower toxicity. There is also a great need for stents that can simultaneously deliver multiple drugs, to treat complex diseases from multiple aspects, or to treat several diseases at the same time. Drug release kinetics greatly determines the stent performance, thus effective strategies should also be developed to achieve customized kinetics.

[1]  U. Siebert,et al.  Randomized comparison of dexamethasone-eluting stents with bare metal stent implantation in patients with acute coronary syndrome: serial angiographic and sonographic analysis. , 2007, American heart journal.

[2]  Shengrong Guo,et al.  5-Fluorouracil-loaded multilayered films for drug controlled releasing stent application: Drug release, microstructure, and ex vivo permeation behaviors. , 2010, Journal of controlled release : official journal of the Controlled Release Society.

[3]  P. Serruys,et al.  Drug-Eluting Stent Update 2007: Part I: A Survey of Current and Future Generation Drug-Eluting Stents: Meaningful Advances or More of the Same? , 2007, Circulation.

[4]  A. Baumbach,et al.  Stent‐based antirestenotic coatings (sirolimus/paclitaxel) , 2002, Catheterization and cardiovascular interventions : official journal of the Society for Cardiac Angiography & Interventions.

[5]  L. Buellesfeld,et al.  ABT-578-Eluting Stents , 2004, Herz.

[6]  Rossella Fattori,et al.  Drug-eluting stents in vascular intervention , 2003, The Lancet.

[7]  N. Krott,et al.  Long-term assessment of a novel biodegradable paclitaxel-eluting coronary polylactide stent. , 2004, European heart journal.

[8]  Liping Tang,et al.  Review: Bioresorbable polymeric stents: current status and future promise , 2003, Journal of biomaterials science. Polymer edition.

[9]  Actinomycin-eluting stent for coronary revascularization: a randomized feasibility and safety study: the ACTION trial. , 2004, Journal of the American College of Cardiology.

[10]  R. Erbel,et al.  Synergistic effects of a novel nanoporous stent coating and tacrolimus on intima proliferation in rabbits , 2003, Catheterization and cardiovascular interventions : official journal of the Society for Cardiac Angiography & Interventions.

[11]  R. Waksman Current state of the absorbable metallic (magnesium) stent. , 2009, EuroIntervention : journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology.

[12]  Patrick W Serruys,et al.  Coronary stents: looking forward. , 2010, Journal of the American College of Cardiology.

[13]  John A Ormiston,et al.  First‐in‐human implantation of a fully bioabsorbable drug‐eluting stent: The BVS poly‐L‐lactic acid everolimus‐eluting coronary stent , 2007, Catheterization and cardiovascular interventions : official journal of the Society for Cardiac Angiography & Interventions.

[14]  S. Çalış,et al.  Development of biodegradable drug releasing polymeric cardiovascular stents and in vitro evaluation , 2009, Journal of microencapsulation.

[15]  O. Bayrak,et al.  A new application for urethral strictures: tacrolimus-eluting stent. , 2010, Journal of endourology.

[16]  P. Serruys,et al.  Biodegradable-polymer-based, paclitaxel-eluting Infinnium stent: 9-Month clinical and angiographic follow-up results from the SIMPLE II prospective multi-centre registry study. , 2006, EuroIntervention : journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology.

[17]  F. Boey,et al.  In vitro and in vivo performance of a dual drug-eluting stent (DDES). , 2010, Biomaterials.

[18]  L. Machan Clinical experience and applications of drug-eluting stents in the noncoronary vasculature, bile duct and esophagus. , 2006, Advanced drug delivery reviews.

[19]  Y. Yoon,et al.  Local Gene Transfer of phVEGF-2 Plasmid by Gene-Eluting Stents: An Alternative Strategy for Inhibition of Restenosis , 2004, Circulation.

[20]  A. Abizaid,et al.  New Drug-Eluting Stents: An Overview on Biodegradable and Polymer-Free Next-Generation Stent Systems , 2010, Circulation. Cardiovascular interventions.

[21]  G. Dangas,et al.  Real world safety and efficacy of the Janus tacrolimus‐eluting stent: Long‐term clinical outcome and angiographic findings from the tacrolimus‐eluting stent (TEST) registry , 2009, Catheterization and cardiovascular interventions : official journal of the Society for Cardiac Angiography & Interventions.

[22]  A. Kastrati,et al.  A polymer-free dual drug-eluting stent in patients with coronary artery disease: a randomized trial vs. polymer-based drug-eluting stents. , 2008, European heart journal.

[23]  P. Mather,et al.  Tailored drug release from biodegradable stent coatings based on hybrid polyurethanes. , 2009, Journal of controlled release : official journal of the Controlled Release Society.

[24]  P. Serruys,et al.  Advances in stent drug delivery: the future is in bioabsorbable stents. , 2009, Expert Opinion on Drug Delivery.

[25]  R. Schwartz,et al.  OrbusNeich fully absorbable coronary stent platform incorporating dual partitioned coatings. , 2009, EuroIntervention : journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology.

[26]  Franz Schwarz,et al.  Comparison of a polymer‐free rapamycin‐eluting stent (YUKON) with a polymer‐based paclitaxel‐eluting stent (TAXUS) in real‐world coronary artery lesions , 2008, Catheterization and cardiovascular interventions : official journal of the Society for Cardiac Angiography & Interventions.

[27]  T. Kurata,et al.  Effectiveness of statin-eluting stent on early inflammatory response and neointimal thickness in a porcine coronary model. , 2008, Circulation journal : official journal of the Japanese Circulation Society.

[28]  G. Reid,et al.  In-vitro activity of triclosan-eluting ureteral stents against common bacterial uropathogens. , 2006, Journal of endourology.

[29]  P. Hwang,et al.  Controlled Steroid Delivery via Bioabsorbable Stent: Safety and Performance in a Rabbit Model , 2009, American journal of rhinology & allergy.

[30]  Sang Joon Park,et al.  Efficacy of a Dexamethasone-Eluting Nitinol Stent on the Inhibition of Pseudointimal Hyperplasia in a Transjugular Intrahepatic Portosystemic Shunt: An Experimental Study in a Swine Model , 2005, Korean journal of radiology.

[31]  Robert C. Eberhart,et al.  Bioresorbable Microporous Stents Deliver Recombinant Adenovirus Gene Transfer Vectors to the Arterial Wall , 1998, Annals of Biomedical Engineering.

[32]  M. Böhm,et al.  Atorvastatin stent coating does not reduce neointimal proliferation after coronary stenting , 2003, Zeitschrift für Kardiologie.

[33]  J. E. Sousa,et al.  Preliminary results of the hydroxyapatite nonpolymer-based sirolimus-eluting stent for the treatment of single de novo coronary lesions a first-in-human analysis of a third-generation drug-eluting stent system. , 2008, JACC. Cardiovascular interventions.

[34]  S. Jain,et al.  Biodegradable-polymer-based, sirolimus-eluting Supralimus stent: 6-month angiographic and 30-month clinical follow-up results from the series I prospective study. , 2008, EuroIntervention : journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology.

[35]  M. Beijk,et al.  XIENCE V everolimus-eluting coronary stent system: a novel second generation drug-eluting stent , 2007, Expert review of medical devices.

[36]  W. Kao,et al.  Drug release kinetics and transport mechanisms of non-degradable and degradable polymeric delivery systems , 2010, Expert opinion on drug delivery.

[37]  D. Holmes Interventional cardiology: A new drug-eluting stent that does not live up to its promise , 2009, Nature Reviews Cardiology.

[38]  J. Gunn,et al.  Stent coatings and local drug delivery; state of the art. , 1999, European heart journal.

[39]  Subbu Venkatraman,et al.  Collapse pressures of biodegradable stents. , 2003, Biomaterials.

[40]  Shengrong Guo,et al.  In vitro and in vivo evaluation of praziquantel loaded implants based on PEG/PCL blends. , 2010, International journal of pharmaceutics.

[41]  M. Hong,et al.  First human experience with angiopeptin‐eluting stent: A quantitative coronary angiography and three‐dimensional intravascular ultrasound study , 2005, Catheterization and cardiovascular interventions : official journal of the Society for Cardiac Angiography & Interventions.

[42]  P. Serruys,et al.  Abstract 5998: Final Results of the HEALING 2B Trial to Evaluate a Bioengineered CD34 Antibody Coated Stent (GenousTMStent) Designed to Promote Vascular Healing by Capture of Circulating Endothelial Progenitor Cells in CAD Patients , 2008 .

[43]  C. Fiori,et al.  Heparin coating on ureteral Double J stents prevents encrustations: an in vivo case study. , 2008, Journal of endourology.

[44]  Shengrong Guo,et al.  A type of esophageal stent coating composed of one 5-fluorouracil-containing EVA layer and one drug-free protective layer: in vitro release, permeation and mechanical properties. , 2007, Journal of controlled release : official journal of the Controlled Release Society.

[45]  A. Connolly,et al.  Introducing the first polymer-free leflunomide eluting stent. , 2008, Atherosclerosis.

[46]  R. Kuntz,et al.  Zotarolimus (ABT-578) eluting stents. , 2006, Advanced drug delivery reviews.

[47]  M. Feldman,et al.  Delivery of paclitaxel from cobalt-chromium alloy surfaces without polymeric carriers. , 2010, Biomaterials.

[48]  Y. Byun,et al.  The short-term effects on restenosis and thrombosis of echinomycin-eluting stents topcoated with a hydrophobic heparin-containing polymer. , 2007, Biomaterials.

[49]  L. P. Tan,et al.  Controlled release of sirolimus from a multilayered PLGA stent matrix. , 2006, Biomaterials.

[50]  N. Kipshidze,et al.  Estrogen‐eluting, phosphorylcholine‐coated stent implantation is associated with reduced neointimal formation but no delay in vascular repair in a porcine coronary model , 2002, Catheterization and cardiovascular interventions : official journal of the Society for Cardiac Angiography & Interventions.

[51]  S. Milz,et al.  Inhibition of Neointima Formation by a Novel Drug-Eluting Stent System That Allows for Dose-Adjustable, Multiple, and On-Site Stent Coating , 2005, Arteriosclerosis, thrombosis, and vascular biology.

[52]  G. Gerken,et al.  Impact of a self-expanding, plastic esophageal stent on various esophageal stenoses, fistulas, and leakages: a single-center experience in 39 patients. , 2005, Gastrointestinal endoscopy.

[53]  P. Fitzgerald,et al.  7-Hexanoyltaxol–Eluting Stent for Prevention of Neointimal Growth: An Intravascular Ultrasound Analysis From the Study to COmpare REstenosis rate between QueST and QuaDS-QP2 (SCORE) , 2002, Circulation.

[54]  M Kellomäki,et al.  Drug-eluting bioabsorbable stents - an in vitro study. , 2009, Acta biomaterialia.

[55]  A randomised comparison of novolimus-eluting and zotarolimus-eluting coronary stents: 9-month follow-up results of the EXCELLA II study. , 2010, EuroIntervention : journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology.

[56]  R. Virmani,et al.  The significance of preclinical evaluation of sirolimus-, paclitaxel-, and zotarolimus-eluting stents. , 2007, The American journal of cardiology.

[57]  T. Tammela,et al.  Biocompatibility, encrustation and biodegradation of ofloxacine and silver nitrate coated poly-L-lactic acid stents in rabbit urethra , 2002, Urological Research.

[58]  P. Serruys,et al.  Final results of the HEALING IIB trial to evaluate a bio-engineered CD34 antibody coated stent (Genous™Stent) designed to promote vascular healing by capture of circulating endothelial progenitor cells in CAD patients. , 2011, Atherosclerosis.

[59]  A. Seth Moving Towards Biomimicry - The Development of the Novel BioMime™ Sirolimus-eluting Coronary Stent System Interventional Cardiology , 2010 .

[60]  K. Schmitz,et al.  In vitro study of drug-eluting stent coatings based on poly(l-lactide) incorporating cyclosporine A – drug release, polymer degradation and mechanical integrity , 2007, Journal of materials science. Materials in medicine.

[61]  G. Stone,et al.  Non–Polymer-Based Paclitaxel-Coated Coronary Stents for the Treatment of Patients With De Novo Coronary Lesions: Angiographic Follow-Up of the DELIVER Clinical Trial , 2004, Circulation.

[62]  L. Buellesfeld,et al.  BioMatrix® Biolimus A9®-eluting coronary stent: a next-generation drug-eluting stent for coronary artery disease , 2006, Expert review of medical devices.

[63]  Changning Guo,et al.  Propagation of uncertainty in nasal spray in vitro performance models using Monte Carlo simulation: Part II. Error propagation during product performance modeling. , 2010, Journal of pharmaceutical sciences.

[64]  J. S. Lee,et al.  Fixation of a Modified Covered Esophageal Stent: Its Clinical Usefulness for Preventing Stent Migration , 2001, Endoscopy.

[65]  E. Verbeken,et al.  Methotrexate loaded SAE coated coronary stents reduce neointimal hyperplasia in a porcine coronary model , 2004, Heart.

[66]  A. Abizaid,et al.  Novolimus™-eluting coronary stent system , 2010 .

[67]  Wonkeun Song,et al.  CTX-M-14 and CTX-M-15 enzymes are the dominant type of extended-spectrum β-lactamase in clinical isolates of Escherichia coli from Korea , 2009, Journal of medical microbiology.

[68]  I. Menown,et al.  Drug-eluting stents: the next generation , 2010 .

[69]  Saibal Kar,et al.  Polymer-Free Biolimus A9–Coated Stent Demonstrates More Sustained Intimal Inhibition, Improved Healing, and Reduced Inflammation Compared With a Polymer-Coated Sirolimus-Eluting Cypher Stent in a Porcine Model , 2010, Circulation. Cardiovascular interventions.

[70]  F. Boey,et al.  In vitro study of release mechanisms of paclitaxel and rapamycin from drug-incorporated biodegradable stent matrices. , 2004, Journal of controlled release : official journal of the Controlled Release Society.

[71]  Jong Chun Park,et al.  Anti-inflammatory Effect of Abciximab-Coated Stent in a Porcine Coronary Restenosis Model , 2007, Journal of Korean medical science.

[72]  Pierfrancesco Agostoni,et al.  The GENESIS (Randomized, Multicenter Study of the Pimecrolimus-Eluting and Pimecrolimus/Paclitaxel-Eluting Coronary Stent System in Patients with De Novo Lesions of the Native Coronary Arteries) trial. , 2009, JACC. Cardiovascular interventions.

[73]  J. Wilcox,et al.  The next generation Endeavor Resolute Stent: role of the BioLinx Polymer System. , 2007, EuroIntervention : journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology.

[74]  Georg Nickenig,et al.  A novel paclitaxel-eluting stent with an ultrathin abluminal biodegradable polymer 9-month outcomes with the JACTAX HD stent. , 2010, JACC. Cardiovascular interventions.

[75]  John D Denstedt,et al.  New developments in ureteral stent design, materials and coatings , 2006, Expert review of medical devices.

[76]  S. Venkatraman,et al.  Adjustable paclitaxel release kinetics and its efficacy to inhibit smooth muscle cells proliferation. , 2008, Journal of controlled release : official journal of the Controlled Release Society.

[77]  S. Venkatraman,et al.  Paclitaxel release from single and double-layered poly(DL-lactide-co-glycolide)/poly(L-lactide) film for biodegradable coronary stent application. , 2008, Journal of biomedical materials research. Part A.

[78]  Frank Litvack,et al.  Local Drug Delivery via a Coronary Stent With Programmable Release Pharmacokinetics , 2003, Circulation.

[79]  Kinam Park,et al.  Mechanisms of controlled drug release from drug-eluting stents. , 2006, Advanced drug delivery reviews.

[80]  W. Wijns,et al.  Differential effects of drug-eluting stents on local endothelium-dependent coronary vasomotion. , 2008, Journal of the American College of Cardiology.

[81]  Outcomes of the tacrolimus drug-eluting Janus stent: a prospective two-centre registry in high-risk patients , 2008, Journal of cardiovascular medicine.

[82]  Fuan Wang,et al.  Layer-by-layer assembly of biologically inert inorganic ions/DNA multilayer films for tunable DNA release by chelation. , 2008, Journal of controlled release : official journal of the Controlled Release Society.

[83]  Na Zhang,et al.  Cationic polymer optimization for efficient gene delivery. , 2010, Mini reviews in medicinal chemistry.

[84]  M. Zilberman,et al.  Drug-eluting bioresorbable stents for various applications. , 2006, Annual review of biomedical engineering.

[85]  Daniel W. Pack,et al.  Design and development of polymers for gene delivery , 2005, Nature Reviews Drug Discovery.

[86]  T. Cheng Origin of the word 'stent'. , 1999, Hospital medicine.

[87]  J. Barry,et al.  The Taxus drug-eluting stent: a new paradigm in controlled drug delivery. , 2006, Advanced drug delivery reviews.

[88]  R. A. Abd El-Baky,et al.  Effect of ciprofloxacin and N-acetylcysteine on bacterial adherence and biofilm formation on ureteral stent surfaces. , 2009, Polish journal of microbiology.

[89]  Dong Ki Lee,et al.  The effect on porcine bile duct of a metallic stent covered with a paclitaxel-incorporated membrane. , 2005, Gastrointestinal endoscopy.

[90]  David P. Martin,et al.  Absorbable polymer stent technologies for vascular regeneration , 2009 .

[91]  W. Roorda,et al.  XIENCE V™ Stent Design and Rationale , 2009 .

[92]  R. Levy,et al.  Gene delivery from a DNA controlled-release stent in porcine coronary arteries , 2000, Nature Biotechnology.

[93]  Ho-Young Song,et al.  Influence of a dexamethasone-eluting covered stent on tissue reaction: an experimental study in a canine bronchial model , 2005, European Radiology.

[94]  T. Tammela,et al.  Urethral in situ biocompatibility of new drug‐eluting biodegradable stents: an experimental study in the rabbit , 2009, BJU international.

[95]  Zhongmin Wang,et al.  In vivo evaluation of 5-fluorouracil-containing self-expandable nitinol stent in rabbits: Efficiency in long-term local drug delivery. , 2010, Journal of pharmaceutical sciences.

[96]  H Shimokawa,et al.  Intramural delivery of a specific tyrosine kinase inhibitor with biodegradable stent suppresses the restenotic changes of the coronary artery in pigs in vivo. , 1998, Journal of the American College of Cardiology.

[97]  Katrin Sternberg,et al.  A Biodegradable Slotted Tube Stent Based on Poly(l-lactide) and Poly(4-hydroxybutyrate) for Rapid Balloon-Expansion , 2007, Annals of Biomedical Engineering.