Surface Modification of Esophageal Stent Materials by a Drug-Eluting Layer for Better Anti-Restenosis Function

Yuxin Bai, Kun Zhang, Ru Xu, Hongtao Liu, Fangxia Guan, Huiwen Luo, Ye Chen, Jingan Li
2018 Coatings  
It is generally accepted that stent implantation is the mainstream therapy in clinics for esophageal cancer in the later period. However, the restenosis caused by tumor cells, epithelial cells, and fibroblasts seriously interferes with the stent medical application and limits its long-term services. To address this conundrum, a series of drug-eluting stents were invented and verified to be feasible in the early stage after implantation, but the limited drug loading and good cell compatibility
more » ... ell compatibility of the stent materials may lead to more serious restenosis and further endanger the patient's life. In previous work, we modified the esophageal stent material 317L stainless steel (317L SS) surface with a poly-dopamine/poly-ethylenimine layer (PDA/PEI), which had strong anti-tumor functions. In this contribution, we employed a usual drug in clinic, 5-fluorouracil (5-Fu), with series of density onto the PDA/PEI modified 317L SS to investigate the influence of 5-Fu immobilization on the anti-restenosis function. The surface characterization including 5-Fu quantity, atomic force microscopy (AFM). Water contact angle measurement indicated successful preparation of the PDA/PEI/5-Fu layers. The spectrophotometric characterization revealed that the immobilized 5-Fu rapidly released over 24 h. However, the Eca109, Het-1A, and L929 cells culture results suggested that the released 5-Fu made a significant contribution to improving the apoptosis and necrosis of these pathological cells, and the PDA/PEI/5-Fu layers maintain the consistent anti-restenosis function on their surfaces with the PDA/PEI layer after 24 h. All the results demonstrated the PDA/PEI/5-Fu layers' excellent ability to suppress esophageal tumor cells, epithelial cells, and fibroblasts, suggesting a potential application on the surface modification of esophageal stents for better anti-restenosis function. covered metal stents. Drug-eluting stents are predominantly used for uncovered stents and this is for a minority of patients who do not tolerate chemotherapy and radiation therapy. Although esophageal drug-eluting stents have the advantage of a certain anti-restenosis function through the release of the loaded drug for in situ therapy [6] [7] [8] , the drug loading on the stent surface is limited, and the stent's anti-restenosis function will gradually lose potency with the drug release [9] . In addition, after the drug release is over, the exposed stent materials, which generally have good biocompatibility, will not only reduce the stent's property of suppressing malignant cells, but also promote their adhesion and excessive proliferation, and this unfavorable for the long-term efficacy of stents [10] . Therefore, it is desirable to develop functional modified layers on continuous anti-restenosis. Layer by layer polymer modification technique is an effective surface modification method for endowing the materials specific functions. Each modified layer can be prepared onto the materials surface with different molecules to achieve different purposes: a poly-dopamine (PDA) layer is usually deposited onto the materials surface as the "double faced adhesive tape" to bind the functional molecules to the materials [11], while poly-ethylenimine (PEI) has been proven to suppress cancer cells in much research [12] . In the previous work, we developed a poly-dopamine/poly-ethylenimine modified layer (PDA/PEI) with strong functions in suppressing esophageal tumor cells [12] . Nevertheless, the PDA/PEI layer's effects on esophageal epithelial cells and fibroblast have still not been investigated because the esophageal restenosis is usually formed by the interaction of the esophageal tumor cells, epithelial cells, and fibroblast [13] . In addition, the PDA/PEI as drug-eluting carrier on the esophageal stent materials (usually 317L stainless steel, 317L SS) should also be considered [14] . 5-fluorouracil (5-Fu) is an effective anti-cancer drug that is widely applied in clinics through the administration of oral, topical, injection, and stent elution [15] . Thus, in this contribution, we immobilized the 5-Fu drug onto the PDA/PEI modified 317L SS surface to investigate the PDA/PEI/5-Fu layers' anti-restenosis function, including suppressing the hypermorphosis of malignant esophageal tumor cells, epithelial cells, and fibroblast.
doi:10.3390/coatings8060215 fatcat:6zmxwyz4qje6bjltwmffr4dv7e