Surface modification by Gas Cluster Ion Beam (GCIB) as a novel drug delivery method for vascular stents

Abstract

Much discussion has focused on the possible inflammatory and thrombogenic influences of the polymer coating on drug‐eluting stents (DES) and the potential for late stent thrombosis. Biodegradable polymers and/or microporous materials are being evaluated by others. In this study, we have used Argon based GCIB to adhere the drug to the surface of a metal. GCIB bombardment results in surface modification of the top 100Å, allowing a thin coating of drug to adhere to the surface without polymer. Titanium foils cut into 1.5cm2 pieces were initially processed with GCIB at 5x1014 Ar clusters/cm2. 50μg of rapamycin (RAP) was placed on the surface; one group received a GCIB drug surface processing while another group did not. Pieces of foil were placed in plasma at 37oC on a rotator to simulate in vivo drug elution for up to 14 days (n=3). Pre‐ and post‐ eluted foils were then placed in plates and 104 mouse endothelial cells were seeded per foil, allowed to attach for 24 hours, and counts were measured by MTS assay. RAP on foils not receiving the second modification by GCIB eluted off within 24 hours and increased cell attachment from 576±403 cells (pre‐eluted) to 8876±1170 (24h post‐eluted, p<0.01). Foils that received a second GCIB modification caused the RAP to be eluted off more slowly, requiring 72 hours before cell attachment matched no‐drug controls (p<0.05). Therefore, GCIB could replace polymers as a drug delivery method for DES.