title: Release of plasmid DNA from intravascular stents coated with ultrathin multilayered polyelectrolyte films.
abstract: Materials that permit control over the release of DNA from the surfaces of topologically complex implantable devices, such as intravascular stents, could contribute to the development of new approaches to the localized delivery of DNA. We report the fabrication of ultrathin, multilayered polyelectrolyte films that permit both the immobilization and controlled release of plasmid DNA from the surfaces of stainless steel intravascular stents. Our approach makes use of an aqueous-based, layer-by-layer method for the assembly of nanostructured thin films consisting of alternating layers of plasmid DNA and a hydrolytically degradable polyamine. Characterization of coated stents using scanning electron microscopy (SEM) demonstrated that stents were coated uniformly with an ultrathin film ca. 120 nm thick that adhered conformally to the surfaces of stent struts. These ultrathin films did not crack, peel, or delaminate substantially from the surface after exposure to a range of mechanical challenges representative of those encountered during stent deployment (e.g., balloon expansion). Stents coated with eight bilayers of degradable polyamine and a plasmid encoding enhanced green fluorescent protein (EGFP) sustained the release of DNA into solution for up to four days when incubated in phosphate buffered saline at 37 degrees C, and coated stents were capable of mediating the expression of EGFP in a mammalian cell line without the aid of additional transfection agents. The approach reported here could, with further development, contribute to the development of localized gene-based approaches to the treatment of cardiovascular diseases or related conditions.
authors.affiliation: Department of Chemical and Biological Engineering, Division of Cardiovascular Medicine, University of Wisconsin-Madison, 1415 Engineering Drive, Madison, Wisconsin 53706, USA.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Jewell
authors.forename: Jingtao
authors.initials: J
authors.lastname: Zhang
authors.forename: Nathaniel J
authors.initials: NJ
authors.lastname: Fredin
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Wolff
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Hacker
authors.forename: David M
authors.initials: DM
authors.lastname: Lynn
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry*; D001709:Biotechnology / Q000379:methods*; D019556:COS Cells; D002522:Chlorocebus aethiops; D020099:Coated Materials, Biocompatible / Q000737:chemistry*; D004247:DNA / Q000737:chemistry*; D004333:Drug Administration Routes; D004573:Electrolytes / Q000737:chemistry*; D049452:Green Fluorescent Proteins / Q000737:chemistry; D008855:Microscopy, Electron, Scanning; D008956:Models, Chemical; D010957:Plasmids / Q000378:metabolism*; D011073:Polyamines / Q000737:chemistry; D015607:Stents
chemical_list: D001672:Biocompatible Materials; D020099:Coated Materials, Biocompatible; D004573:Electrolytes; D011073:Polyamines; D049452:Green Fluorescent Proteins; D004247:DNA