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Local perivascular delivery of anti-restenotic agents from a drug-eluting poly(ε-caprolactone) stent cuff

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Author: Pires, N.M.M. · Hoeven, B.L. van der · Vries, M.R. de · Havekes, L.M. · Vlijmen, B.J. van · Hennink, W.E. · Quax, P.H.A. · Jukema, J.W.
Institution: TNO Kwaliteit van Leven
Source:Biomaterials, 26, 26, 5386-5394
Identifier: 238698
doi: DOI:10.1016/j.biomaterials.2005.01.063
Keywords: Biology · Biomedical Research · Animal model · Controlled drug release · Drug-eluting stents · Local delivery · Poly(ε-caprolactone) · Restenosis · Cardiology · Cell culture · Mathematical models · Muscle · Anti-restenotic agents · Contralateral femoral arteries · Drug-eluting stents (DES) · Interventional cardiology · Controlled drug delivery · Actin · Macrogol 300 · Macrogol derivative · Paclitaxel · Polycaprolactone · Polymer · Rapamycin · Unclassified drug · Animal experiment · Animal tissue · Artery intima proliferation · controlled study · Dose response · Drug delivery system · Drug formulation · Femoral artery · In vivo study · In-stent restenosis · Mouse · Nonhuman · Reproducibility · Smooth muscle fiber · Sustained drug release · Animals · Blood Vessel Prosthesis · Coated Materials, Biocompatible · Diffusion · Drug Carriers · Drug Implants · Femoral Artery · Graft Occlusion, Vascular · Immunosuppressive Agents · Male · Materials Testing · Mice · Mice, Inbred C57BL · Paclitaxel · Polyesters · Sirolimus · Stents · Animalia


The introduction of drug-eluting stents (DES) to prevent in-stent restenosis is one of the major advances in interventional cardiology. Currently many types of DES are under evaluation for effectiveness and safety, a time-consuming and difficult procedure in humans. An animal model that allows rapid evaluation of the present and upcoming therapeutic approaches to prevent in-stent restenosis is most valuable and still lacking. Here, a perivascular cuff to induce restenosis was constructed of a poly(ε-caprolactone) (PCL) formulation suitable for the controlled delivery of drugs. Placing the PCL cuff around the femoral artery, in vivo, resulted in reproducible restenosis-like lesions containing predominantly smooth muscle-actin positive cells. Loading the cuff with the anti-restenotic compounds paclitaxel and rapamycin resulted, in vitro, in a sustained and dose-dependent release for at least 3 weeks. Paclitaxel- and rapamycin-eluting PCL cuffs placed around the femoral artery of mice in vivo significantly reduced intimal thickening by 76±2% and 75±6%, respectively, at 21 days. Perivascular sustained release of both anti-restenotic agents is restricted to the cuffed vessel segment with no systemic adverse effects or effect on cuffed contralateral femoral arteries. Drug-eluting PCL cuffs provide an easy and rapid tool to evaluate anti-restenotic agents to be used in combination with the DES strategies. © 2005 Elsevier Ltd. All rights reserved. Chemicals / CAS: macrogol 300, 37361-15-2; paclitaxel, 33069-62-4; polycaprolactone, 24980-41-4, 25248-42-4; rapamycin, 53123-88-9; aquaplast, caprolactone, 24980-41-4; Coated Materials, Biocompatible; Drug Carriers; Drug Implants; Immunosuppressive Agents; Paclitaxel, 33069-62-4; Polyesters; Sirolimus, 53123-88-9