Novel bioabsorbable salicylate-based polymer as a drug-eluting stent coating.
BACKGROUND
Permanent polymers used in current drug-eluting stents (DES) can trigger chronic inflammation and hypersensitivity reactions, which may contribute to the increased risk of late thrombosis and rebound restenosis. Therefore, optimal polymer selection and the use of completely absorbable but biocompatible polymers are expected to minimize these risks.


OBJECTIVE
We sought to evaluate a novel, potentially innately anti-inflammatory, bioabsorbable salicylate-based polymer as a DES coating, in a clinically relevant animal model.


METHODS
Four types of stents were implanted in pig coronary arteries using QCA to optimize stent apposition: bare metal stents (BMS); salicylic acid/adipic acid bioabsorbable polymer-only coated metal stents (SA/AA); biostable polymeric sirolimus-eluting stents (Cypher); and metal stents coated with salicylic acid/adipic acid bioabsorbable polymer containing sirolimus (SA/AA + S). The dose density of sirolimus was 8.3 microg/mm of stent length (similar to Cypher) with in vitro studies demonstrating elution over 30 days and complete polymer degradation in 37 days. Animals underwent angiographic restudy and were terminated at 1 month for complete histopathologic and histomorphometric analyses.


RESULTS
Both SA/AA + S and Cypher stents had significantly lower angiographic % stenosis when compared with BMS and SA/AA polymer-only groups (6 +/- 4% and 5 +/- 4% vs. 15 +/- 7% and 16 +/- 5%, respectively, P < 0.001). Intimal thickness was lower for SA/AA + S and Cypher than for BMS (0.14 +/- 0.06 and 0.13 +/- 0.04 mm vs. 0.23 +/- 0.05 mm, respectively, P < 0.001). Histologic % area stenosis was also lower for SA/AA + S and Cypher when compared with BMS (22 +/- 7% and 23 +/- 6% vs. 33 +/- 5%, respectively, P < 0.001). There was a strong trend toward reduced inflammatory response in the SA/AA and SA/AA + S when compared with BMS and Cypher groups (P = 0.072).


CONCLUSIONS
This study shows favorable vascular compatibility and efficacy for a novel bioabsorbable salicylate-based polymer as a DES coating, and supports further research and development of this unique class of polymer materials for applications in cardiovascular devices.
Jabara
Refat
R
Saint Joseph's Translational Research Institute, Saint Joseph's Hospital of Atlanta, Atlanta, Georgia 30342, USA. rjabara@sjha.org
Chronos
Nicolas
N
Robinson
Keith
K
D000042:Absorption; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal; D020099:Coated Materials, Biocompatible / Q000009:adverse effects / Q000493:pharmacokinetics; D017023:Coronary Angiography; D003331:Coronary Vessels / Q000473:pathology; D054855:Drug-Eluting Stents / Q000009:adverse effects; D008670:Metals; D011108:Polymers / Q000138:chemical synthesis; D012459:Salicylates; D020123:Sirolimus / Q000493:pharmacokinetics; D015607:Stents; D034421:Sus scrofa; D017539:Tunica Intima / Q000473:pathology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D020099:Coated Materials, Biocompatible; D008670:Metals; D011108:Polymers; D012459:Salicylates; D020123:Sirolimus