REDV/Rapamycin-loaded polymer combinations as a coordinated strategy to enhance endothelial cells selectivity for a stent system

Abstract

A major challenge in the development of drug eluting stent platform is the sustained inhibition of smooth muscle cell (SMC) proliferation while endothelial cell (EC) coverage is promoted. We demonstrated in this study that the combination of rapamycin-loaded polymer base layer and Arg-Glu-Asp-Val (REDV) peptide tethered top layer is a coordinated strategy to enhance EC-specific selectivity. A 2-methacryloyloxyethyl phosphorylcholine(MPC)-co-n-stearyl methacrylate (SMA) [PMS] film was prepared as a base coating to load rapamycin. MPC-co-SMA-co-p-nitrophenyloxycarbonyl polyethyleneglycol methacrylate (MEONP) [PMSN] was synthesized to form the top layer, which conjugated the EC-specific ligand REDV peptide that promotes EC attachment. The top layer functioned as a diffusion barrier, and the polymer film can sustain the rapamycin release of for over 120 days. The In vitro cell behavior of EC and SMC indicated that the rapamycin loaded polymer film inhibited cell growth in the first few days of drug release. After 8 days of drug release, the composite coating consistently resisted the nonspecific adsorption of SMC, whereas REDV enhanced EC attachment specifically. A rabbit iliac injury model was used to evaluate the in vivo of the application of this kind of surface-modified stainless steel stent. The composite polymer coating approach could significantly promote re-endothelialization without causing neointimal hyperplasia. The combination of an EC-specific ligand with rapamycin-loaded polymeric coating may potentially be an effective therapeutic alternative to improve currently available drug-eluting stents.