Arafat Mohammad, Fouladian Paris, Wignall Anthony, Song Yunmei, Parikh Ankit, Albrecht Hugo, Prestidge Clive A, Garg Sanjay, Blencowe Anton
Pharmaceutical Innovation and Development (PIDG) Group, Clinical and Health Sciences, University of South Australia (UniSA), Adelaide, SA 5000, Australia.
ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Clinical and Health Sciences, University of South Australia (UniSA), Adelaide, SA 5000, Australia.
Pharmaceutics. 2020 Dec 24;13(1):17. doi: 10.3390/pharmaceutics13010017.
Self-expanding metal stents (SEMSs) are currently the gold standard for the localised management of malignant gastrointestinal (GI) stenosis and/or obstructions. Despite encouraging clinical success, in-stent restenosis caused by tumour growth is a significant challenge. Incorporating chemotherapeutic drugs into GI stents is an emerging strategy to provide localised and sustained release of drugs to intestinal malignant tissues to prevent tumour growth. Therefore, the aim of this work was to develop and evaluate a local GI stent-based delivery system that provides a controlled release of 5-fluorouracil (5FU) over a course of several weeks to months, for the treatment of colorectal cancer and cancer-related stenosis/obstructions. The 5FU-loaded GI stents were fabricated via sequential dip-coating of commercial GI stents with a drug-loaded polyurethane (PU) basecoat and a drug-free poly(ethylene--vinyl acetate) (PEVA) topcoat. For comparison, two types of commercial stents were investigated, including bare and silicone (Si) membrane-covered stents. The physicochemical properties of the 5FU-loaded stents were evaluated using photoacoustic Fourier-transform infrared (PA-FTIR) spectroscopy, X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), and thermal analysis. In vitro release studies in biological medium revealed that the 5FU-loaded stents provided a sustained release of drug over the period studied (18 d), and cell viability, cell cycle distribution and apoptosis assays showed that the released 5FU had comparable anticancer activity against human colon cancer cells (HCT-116) to pure 5FU. This study demonstrates that dip-coating is a facile and reliable approach for fabricating drug-eluting stents (DESs) that are promising candidates for the treatment of GI obstructions and/or restenosis.
自膨式金属支架（SEMSs）目前是局部治疗恶性胃肠道（GI）狭窄和/或梗阻的金标准。尽管临床取得了令人鼓舞的成功，但肿瘤生长导致的支架内再狭窄仍是一个重大挑战。将化疗药物融入胃肠道支架是一种新兴策略，可将药物局部且持续地释放到肠道恶性组织中以防止肿瘤生长。因此，本研究的目的是开发并评估一种基于局部胃肠道支架的给药系统，该系统能在数周至数月的时间内实现5-氟尿嘧啶（5FU）的控释，用于治疗结直肠癌以及癌症相关的狭窄/梗阻。通过依次用载药聚氨酯（PU）底涂层和无药聚（乙烯-醋酸乙烯酯）（PEVA）顶涂层对商用胃肠道支架进行浸涂来制备载5FU的胃肠道支架。为作比较，研究了两种商用支架，包括裸支架和硅胶（Si）膜覆盖支架。使用光声傅里叶变换红外（PA-FTIR）光谱、X射线衍射（XRD）、X射线光电子能谱（XPS）、扫描电子显微镜（SEM）和热分析对载5FU支架的物理化学性质进行了评估。在生物介质中的体外释放研究表明，载5FU支架在所研究的时间段（18天）内实现了药物的持续释放，细胞活力、细胞周期分布和凋亡分析表明，释放出的5FU对人结肠癌细胞（HCT-116）的抗癌活性与纯5FU相当。本研究表明，浸涂是一种简便可靠的制备药物洗脱支架（DESs）的方法，这些支架有望用于治疗胃肠道梗阻和/或再狭窄。
