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A 5-fluorouracil-loaded polydioxanone weft-knitted stent for the treatment of colorectal cancer

2013; Elsevier BV; Volume: 34; Issue: 37 Linguagem: Inglês

10.1016/j.biomaterials.2013.08.055

1878-5905

Gang Li, Yufeng Chen, Jun Hu, Xiaojian Wu, Junyan Hu, Xiaowen He, Jiashen Li, Zheng Zhao, Zexian Chen, Yuling Li, Hong Hu, Yi Li, Ping Lan,

Colorectal and Anal Carcinomas

In-stents restenosis caused by tumour ingrowth is a major problem for patients undergoing stent displacement because the conventional stents often lack a sustained anti-tumour capability. The aim of this paper was to develop a weft-knitted polydioxanone stent which can slow release 5-fluorouracil (5-FU). In order to determine the most suitable drug concentration, the 5-FU safe concentration in vivo and appropriate loading percentage in the membranes were investigated, and then 5-FU-loaded poly-l-lactide membranes at concentration of 3.2%, 6.4% and 12.8% were coated onto the stent using electro-spinning method, respectively. The morphology, chemical structure and in vitro drug release property of the coating membranes were subsequently examined. Their anti-tumour activity and mechanism were assessed in vitro and in vivo using a human colorectal cancer cell line HCT-116 and tumour-bearing BALB/c nude mice. The half maximal inhibitory concentration (IC50) and the median lethal dose (LD50) demonstrated that the 6.4% and 12.8% membranes had better anti-tumour effects than pure 5-FU due to the sustainable drug releasing property of the coated membranes on the stent. The membranes possessing appropriate drug loading doses, such as 6.4% or 12.8% also provided better anti-in-stents restenosis effects than other groups tested. Therefore, it is concluded that the drug-loaded stents have great potential for the use in the treatment of intestinal cancers in the future.