Local perivascular delivery of anti-restenotic agents from a drug-eluting poly(ε-caprolactone) stent cuff
article
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
Topics
Biomedical 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
TNO Identifier
238698
ISSN
01429612
Source
Biomaterials, 26(26), pp. 5386-5394.
Pages
5386-5394
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