Development of high-performance stent: gelatinous photogel-coated stent that permits drug delivery and gene transfer.
Hydrogel-coated metallic stents may provide supplementary functions such as local drug delivery and gene transfer in addition to mechanical dilation function. To this end, we used a photoreactive material consisting of gelatin macromer (multiple styrene-derivatized gelatin) and carboxylated camphorquinone (photo-initiator). A few minutes of visible light irradiation of a stent after dip-coating of an aqueous solution of the photoreactive material resulted in the formation of a homogeneously crosslinked gelatinous layer on the entire exterior surface of the stent. As the metal stent, gold stents under development were used. Rhodamine-conjugated albumin as a model drug or adenoviral vector expressing bacterial beta-galactosidase (AdLacZ) as a model gene were photo-immobilized in the gelatinous gel layer. In vitro experiments using hybrid tubular tissue, which is a self-shrinkaged, vascular smooth muscle cell-incorporated type-I collagen gel, as a vascular model, showed that the immobilized dye-derivatized albumin was released on and permeated into tissues, as observed by confocal laser microscopy, and that the cells transfected with immobilized AdLacZ produced beta-galactosidase up to almost 3 weeks, as observed by x-gal staining. In preliminary in vivo experiments these drug- or adenovirus-immobilized stents were implanted in rabbit common carotid arteries. Within 3 weeks of implantation, drug permeation and gene expression in the vascular tissues were observed, indicating that the gelatinous photogel effectively serves as a matrix or coating for a bioactive stent,which permits drug release as well as gene transfer. This intraluminal approach has the potential to realize drug and gene therapy in atherosclerotic plaque.
Nakayama
Y
Y
Department of Bioengineering, National Cardiovascular Center Research Institute, Japan.
Ji-Youn
K
K
Nishi
S
S
Ueno
H
H
Matsuda
T
T
D000418:Albumins / Q000008:administration & dosage; D000818:Animals; D002339:Carotid Arteries; D020099:Coated Materials, Biocompatible; D046508:Culture Techniques; D016503:Drug Delivery Systems / Q000295:instrumentation*; D018014:Gene Transfer Techniques / Q000295:instrumentation*; D020100:Hydrogels / Q000737:chemistry*; D007763:Lac Operon; D008027:Light; D018613:Microscopy, Confocal; D008855:Microscopy, Electron, Scanning; D015394:Molecular Structure; D009131:Muscle, Smooth, Vascular; D011817:Rabbits; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012235:Rhodamines / Q000008:administration & dosage; D015607:Stents; D001616:beta-Galactosidase / Q000378:metabolism
D000418:Albumins; D020099:Coated Materials, Biocompatible; D020100:Hydrogels; D011993:Recombinant Fusion Proteins; D012235:Rhodamines; D001616:beta-Galactosidase