A Promising Approach for Improving the Coating Stability and In Vivo Performance of Biodegradable Polymer-Coated Sirolimus-Eluting Stent

Abstract

Several developments are in progress for improving the performance of drug-eluting stents (DESs) including use of biodegradable polymers, polymer-free DES, fully bioabsorbable stents, and so on. The commercially available DESs still suffer from polymer defects that could affect the performance of a DES through a series of adverse events such as coating delamination and/ or peeling-off that lead to non-uniform local drug distribution, restenosis, and thrombosis. The goal of this work was to enhance the stability of drug-in-polymer matrix coating on a stent metal surface through surface modification. The cobalt-chromium (Co-Cr) surface was chemically modified using poly(dopamine) (PDA) nano-coating and poly(L-lactide) (PLLA) nano-brush in order to be applied to a biodegradable polymer-coated DES. The biodegradable polymer loaded with sirolimus was coated using an ultrasonic spray coating instrument. The coating morphology on all samples showed a very smooth and uniform coating. The stability of the coating was evaluated for 2 months under the circulation system in which the drug-in-polymer coating on the PLLA brush-modified stent presented the most stable coating behavior as compared to other samples. The in vitro sirolimus release study from both unmodified and modified stents was studied in phosphate-buffered saline (PBS), and the modified stents showed slower sirolimus release profile as compared to unmodified stents. In vivo study was performed in a porcine coronary artery injury model for 28 days. The percentage of in-stent restenosis area (ISR) for PLLA brush-modified sirolimus-eluting stent (SES) decreased significantly as compared to unmodified SES and bare metal stent (BMS). This study demonstrated that the modification of stent surface using PLLA brushes affects in vitro and in vivo performance effectively to be applied for biodegradable polymercoated DES.