title: Radionuclides-hyaluronan-conjugate thromboresistant coatings to prevent in-stent restenosis.
abstract: Catheter-based brachytherapy is one of the most effective modalities to inhibit hyperplasia following revascularization procedures. Radioactive stents have failed, however, to prevent clinical hyperplasia due to excessive late lumen loss on the edge of the devices. Numerous strategies have been proposed to circumvent the drawbacks of irradiation therapies, such as the use of more appropriate radionuclides or the "hot-end" stents approach. This paper describes versatile radioactive devices obtained by coating plasma functionalized surfaces-stents or catheters-with a hyaluronan (HA)-diethylenetriamine pentaacetic acid (DTPA) conjugate (HA-DTPA) complexed with a gamma or beta radionuclide. Yttrium and indium were used as radionuclide models, due to their suitability for endovascular radiotherapy. X-ray photoelectron microscopy and time-of-flight secondary ions mass spectrometry analyses confirmed the successful immobilization of the HA-DTPA conjugate on both the metallic (NiTi) and polymeric (Teflon) plasma functionalized surfaces. HA-DTPA-coated surfaces were significantly more hydrophilic than bare surfaces (39.5 degrees vs. 67 degrees on NiTi substrate and 29 degrees vs. 128 degrees on Teflon substrate). Therapeutic doses of yttrium and indium were easily loaded onto the surfaces and remained stable over 2 weeks with a radionuclide loss of about 6%. The HA-DTPA-coated Teflon surfaces presented significantly less fibrinogen adsorption than uncoated materials in an in vitro flow model. This approach, which combines the hemocompatibility of HA-coated surfaces and the anti-proliferative effects of an appropriate radiotherapy, constitutes a promising methodology to alleviate the restenosis induced by existing devices.
authors.affiliation: Department of Biomedical Engineering, Mc Gill University, 3775 University Street, Montreal, Que., Canada H3A 2B4.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Thierry
authors.forename: Françoise M
authors.initials: FM
authors.lastname: Winnik
authors.forename: Yahye
authors.initials: Y
authors.lastname: Merhi
authors.forename: Jim
authors.initials: J
authors.lastname: Silver
authors.forename: Maryam
authors.initials: M
authors.lastname: Tabrizian
mesh_terms: D000327:Adsorption; D001807:Blood Vessel Prosthesis / Q000009:adverse effects; D001918:Brachytherapy / Q000379:methods*; D020099:Coated Materials, Biocompatible / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D005240:Feasibility Studies; D005340:Fibrinogen / Q000737:chemistry; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000737:chemistry; D006083:Graft Occlusion, Vascular / Q000209:etiology / Q000517:prevention & control / Q000532:radiotherapy*; D006820:Hyaluronic Acid / Q000008:administration & dosage* / Q000737:chemistry*; D008422:Materials Testing; D004369:Pentetic Acid / Q000737:chemistry*; D011485:Protein Binding; D011868:Radioisotopes / Q000627:therapeutic use*; D015607:Stents / Q000009:adverse effects*; D013499:Surface Properties
chemical_list: D020099:Coated Materials, Biocompatible; D005343:Fibrinolytic Agents; D011868:Radioisotopes; D004369:Pentetic Acid; D005340:Fibrinogen; D006820:Hyaluronic Acid