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Synergistic effects of a novel nanoporous stent coating and tacrolimus on intima proliferation in rabbits
Author(s) -
Wieneke Heinrich,
Dirsch Olaf,
Sawitowski Thomas,
Gu Yan Li,
Brauer Holger,
Dahmen Uta,
Fischer Alfons,
Wnendt Stefan,
Erbel Raimund
Publication year - 2003
Publication title -
catheterization and cardiovascular interventions
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.988
H-Index - 116
eISSN - 1522-726X
pISSN - 1522-1946
DOI - 10.1002/ccd.10664
Subject(s) - neointima , nanoporous , medicine , tacrolimus , coating , stent , restenosis , ceramic , materials science , biomedical engineering , surgery , composite material , nanotechnology , transplantation
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 μg (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 μg (P = 0.047) and 56% for 120 μg (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. Catheter Cardiovasc Interv 2003;60:399–407. © 2003 Wiley‐Liss, Inc.

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