Comparison of polymer-coated, drug-eluting self-expandable metal stents for the potential treatment of gastrointestinal cancers

Abstract

Self-expandable metal stents (SEMS) represent the gold standard for the clinical management of malignant obstructions in the gastrointestinal tract. Gastrointestinal stent blockage (restenosis) caused by tumour growth is a common problem. The incorporation of anticancer drugs into SEMS for localised delivery could potentially address restenosis, although further studies are required to better understand the influence of the stent structure in combination with different drug-eluting polymer formulations and chemotherapeutics. Therefore, in this work, we investigated for the first time the suitability of a polyurethane-silicone (PUS) elastomer for the controlled encapsulation and release of 5-fluorouracil (5FU) from membrane-covered oesophageal stents (OS) and bare enteral colonic stents (CS). The stents were coated with a bilayer structure consisting of a 5FU-loaded (7.0% w/w) PUS basecoat and poly(ethylene-co-vinyl acetate) (PEVA) diffusion regulating topcoat. Physicochemical characterisation of the coatings revealed that 5FU is uniformly distributed and semi-crystalline in the PUS layer, and that 5FU did not leach into the topcoat during coating. Interestingly, drug release from the coated stents revealed a significant difference, with 5FU release from CS plateauing after ∼12 d, while a much more gradual release was observed with the OS over 150 d. Imaging revealed that defects in the coatings due to the underlying stent structure are likely contributors to these differences. The coated stents were found to be stable to gamma sterilisation and in accelerated stability tests. In vitro cytotoxicity, cell cycle and apoptosis assays revealed that 5FU released from the stents had comparable anticancer efficacy to free 5FU against human colon carcinoma cells. This research demonstrates the potential of polymer-coated SEMS for controlled drug-release and highlights the importance of the underlying stent structure on performance.