Low-dose paclitaxel elution by novel bioerodible sol-gel coating on stents inhibits neointima with low toxicity in porcine coronary arteries.
OBJECTIVE
The present study was designed to evaluate a novel bioerodible sol-gel film coated paclitaxel-eluting stent (sol-gel-PES, 3 microg per stent) in a porcine coronary artery model.


BACKGROUND
Although current polymer-based PES decrease restenosis, the permanent polymer and bound drug have raised concerns regarding delayed vessel healing and late stent thrombosis.


METHODS
Polymer-based PES (poly-PES, n = 8), sol-gel-PES (n = 15), bare metal (BMS, n = 14), and sol-gel film only (sham, n = 12), stents were implanted in 17 juvenile pigs. Animals were terminated 28 days post-implant for angiographic restudy and complete histopathologic and histomorphometric analyses.


RESULTS
Angiographic late loss was equally reduced for both poly-PES and sol-gel-PES (0.51 +/- 0.64 and 0.61 +/- 0.52 mm, respectively) compared to both BMS and sham (0.98 +/- 0.74 and 1.25 +/- 0.72 mm, p < 0.05). Similarly beneficial results were observed for histomorphometric parameters of neointimal thickness and area, yielding reductions of in-stent stenosis by 43% and 48% for poly-PES, as well as 31% and 37% for sol-gel-PES, vs. BMS and sham, respectively (p < 0.05). Re-endothelialization was complete in all groups. Although the inflammatory cell infiltration and intramural thrombus scores were no different between poly- and sol-gel-PES, medial necrosis was increased for poly-PES (p < 0.05 vs. all others).


CONCLUSIONS
A novel bioerodible sol-gel film coated with low-dose paclitaxel demonstrates less toxicity to the coronary tunica media, while retaining effective inhibition of neointimal formation at 28 days.
Shinke
Toshiro
T
Saint Joseph's Translational Research Institute/Saint Joseph's Hospital of Atlanta, GA 30342, USA.
Geva
Sarah
S
Pendyala
Lakshmana
L
Jabara
Refat
R
Li
Jinsheng
J
Chen
Jack P
JP
Venegoni
Anna
A
Colley
Kenneth
K
Klein
Richard
R
Chronos
Nicolas
N
Robinson
Keith
K
Hou
Dongming
D
D000818:Animals; D017023:Coronary Angiography; D023903:Coronary Restenosis / Q000517:prevention & control*; D003331:Coronary Vessels / Q000187:drug effects* / Q000473:pathology*; D004305:Dose-Response Relationship, Drug; D054855:Drug-Eluting Stents; D005260:Female; D005782:Gels; D008297:Male; D009336:Necrosis; D017239:Paclitaxel / Q000493:pharmacokinetics* / Q000633:toxicity; D011108:Polymers; D034421:Sus scrofa; D050257:Tubulin Modulators / Q000493:pharmacokinetics* / Q000633:toxicity; D017539:Tunica Intima / Q000187:drug effects / Q000473:pathology
D005782:Gels; D011108:Polymers; D050257:Tubulin Modulators; D017239:Paclitaxel