Print Email Facebook Twitter Local perivascular delivery of anti-restenotic agents from a drug-eluting poly(ε-caprolactone) stent cuff Title Local perivascular delivery of anti-restenotic agents from a drug-eluting poly(ε-caprolactone) stent cuff Author Pires, N.M.M. van der Hoeven, B.L. de Vries, M.R. Havekes, L.M. van Vlijmen, B.J. Hennink, W.E. Quax, P.H.A. Jukema, J.W. TNO Kwaliteit van Leven Publication year 2005 Abstract 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 Subject BiologyBiomedical ResearchAnimal modelControlled drug releaseDrug-eluting stentsLocal deliveryPoly(ε-caprolactone)RestenosisCardiologyCell cultureMathematical modelsMuscleAnti-restenotic agentsContralateral femoral arteriesDrug-eluting stents (DES)Interventional cardiologyControlled drug deliveryActinMacrogol 300Macrogol derivativePaclitaxelPolycaprolactonePolymerRapamycinUnclassified drugAnimal experimentAnimal tissueArtery intima proliferationcontrolled studyDose responseDrug delivery systemDrug formulationFemoral arteryIn vivo studyIn-stent restenosisMouseNonhumanReproducibilitySmooth muscle fiberSustained drug releaseAnimalsBlood Vessel ProsthesisCoated Materials, BiocompatibleDiffusionDrug CarriersDrug ImplantsFemoral ArteryGraft Occlusion, VascularImmunosuppressive AgentsMaleMaterials TestingMiceMice, Inbred C57BLPaclitaxelPolyestersSirolimusStentsAnimalia To reference this document use: http://resolver.tudelft.nl/uuid:365bf69f-f582-425b-983d-c544d2340d25 DOI https://doi.org/10.1016/j.biomaterials.2005.01.063 TNO identifier 238698 ISSN 0142-9612 Source Biomaterials, 26 (26), 5386-5394 Document type article Files To receive the publication files, please send an e-mail request to TNO Library.