title: Perivascular sirolimus-delivery system.
abstract: Autologous vein grafts are often used for treating damaged vessels, e.g. arteriovenous fistulas or arterial bypass conduits. Veins have a different histological structure from arteries, which often leads to intimal hyperplasia and graft restenosis. The aim of this study was to develop a perivascular sirolimus-delivery system that would release the antiproliferative drug sirolimus in a controlled manner. Polyester Mesh I was coated with purasorb, i.e. a copolymer of L-lactide and ɛ-caprolactone, with dissolved sirolimus; Mesh II was coated with two copolymer layers; the layer with dissolved sirolimus was overlaid with pure purasorb. This arrangement allowed sirolimus to be released for 6 and 4 weeks, for Mesh I and Mesh II, respectively. Mesh II released sirolimus more homogeneously, without the initial burst effect during the first week. However, the cumulative release curve was steeper at later time points than the curve for Mesh I. Both meshes inhibited proliferation of rat vascular smooth muscle cells during 14-day culture in vitro and preserved excellent cell viability. Newly developed sirolimus-releasing perivascular meshes are promising devices for preventing autologous graft restenosis.
authors.affiliation: Institute of Physiology, Academy of Sciences of the Czech Republic, vvi Videnska 1083, 142 20 Prague 4, Czech Republic. filova@biomed.cas.cz
authors.forename: Elena
authors.initials: E
authors.lastname: Filova
authors.forename: Martin
authors.initials: M
authors.lastname: Parizek
authors.forename: Jana
authors.initials: J
authors.lastname: Olsovska
authors.forename: Zdenek
authors.initials: Z
authors.lastname: Kamenik
authors.forename: Eduard
authors.initials: E
authors.lastname: Brynda
authors.forename: Tomas
authors.initials: T
authors.lastname: Riedel
authors.forename: Marta
authors.initials: M
authors.lastname: Vandrovcova
authors.forename: Vera
authors.initials: V
authors.lastname: Lisa
authors.forename: Ludka
authors.initials: L
authors.lastname: Machova
authors.forename: Ivo
authors.initials: I
authors.lastname: Skalsky
authors.forename: Ondrej
authors.initials: O
authors.lastname: Szarszoi
authors.forename: Tomas
authors.initials: T
authors.lastname: Suchy
authors.forename: Lucie
authors.initials: L
authors.lastname: Bacakova
mesh_terms: D000818:Animals; D002317:Cardiovascular Agents / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D020099:Coated Materials, Biocompatible; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D004339:Drug Compounding; D004355:Drug Stability; D006083:Graft Occlusion, Vascular / Q000517:prevention & control; D007700:Kinetics; D008297:Male; D008855:Microscopy, Electron, Scanning; D008970:Molecular Weight; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D032389:Myocytes, Smooth Muscle / Q000187:drug effects; D011091:Polyesters / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D020123:Sirolimus / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology; D012995:Solubility; D013499:Surface Properties; D013678:Technology, Pharmaceutical / Q000379:methods
chemical_list: D002317:Cardiovascular Agents; D020099:Coated Materials, Biocompatible; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D011091:Polyesters; C062968:lactide-caprolactone copolymer; D020123:Sirolimus