Synergistic effects of a novel nanoporous stent coating and tacrolimus on intima proliferation in rabbits.
To overcome the problem of in-stent restenosis, the concept of local delivery of antiproliferative or immunosuppressive drugs has been introduced into interventional cardiology. Local drug delivery can be achieved by drug-eluting stents coated with polymer surfaces used for controlled drug release. However, several polymer coatings have shown an induction of inflammatory response and increased neointima formation. In the present study, the effect of a new inorganic ceramic nanoporous aluminum oxide (Al(2)O(3)) coating on neointima proliferation and its suitability as a carrier for the immunosuppressive drug tacrolimus have been investigated. 316 L stainless steel coronary stents were coated with a 500 nm thin nanoporous aluminum oxide layer. This ceramic nanolayer was used as a carrier for tacrolimus. Bare stents (n = 6), ceramic coated stents (n = 6), and ceramic coated stents loaded with 60 (n = 7) and 120 mug (n = 6) tacrolimus were implanted in the common carotid artery of New Zealand rabbits. The ceramic coating caused no significant reduction of neointimal thickness after 28 days. Loading the ceramic stents with tacrolimus led to a significant reduction of neointima thickness by 52% for 60 mug (P = 0.047) and 56% for 120 mug (P = 0.036) as compared to the bare stents. The ceramic coating alone as well as in combination with tacrolimus led to a reduced infiltration of lymphocytes and macrophages in the intima in response to stent implantation. Ceramic coating of coronary stents with a nanoporous layer of aluminum oxide in combination with tacrolimus resulted in a significant reduction in neointima formation and inflammatory response. The synergistic effects of the ceramic coating and tacrolimus suggest that this new approach may have a high potential to translate into clinical benefit.
Wieneke
Heinrich
H
Department of Cardiology, University Essen, Essen, Germany. heinrich.wieneke@uni-essen.de
Dirsch
Olaf
O
Sawitowski
Thomas
T
Gu
Yan Li
YL
Brauer
Holger
H
Dahmen
Uta
U
Fischer
Alfons
A
Wnendt
Stefan
S
Erbel
Raimund
R
D000818:Animals; D019917:Blood Vessel Prosthesis Implantation; D017536:Carotid Artery, Common / Q000473:pathology / Q000601:surgery / Q000648:ultrastructure; D002516:Ceramics / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D020099:Coated Materials, Biocompatible / Q000378:metabolism / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004867:Equipment Design / Q000295:instrumentation; D005260:Female; D006083:Graft Occlusion, Vascular / Q000517:prevention & control; D007166:Immunosuppressive Agents / Q000097:blood / Q000494:pharmacology*; D008297:Male; D008854:Microscopy, Electron; D008955:Models, Cardiovascular; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D011817:Rabbits; D015607:Stents; D016559:Tacrolimus / Q000097:blood* / Q000494:pharmacology*; D017539:Tunica Intima / Q000187:drug effects* / Q000473:pathology* / Q000648:ultrastructure
D020099:Coated Materials, Biocompatible; D007166:Immunosuppressive Agents; D016559:Tacrolimus