Development and In Vitro Evaluation of 5-Fluorouracil-Eluting Stents for the Treatment of Colorectal Cancer and Cancer-Related Obstruction

Abstract

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-co-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.

Hydroxypropyl methylcellulose/graphene oxide composite as drug carrier system for 5‐fluorouracil

“…This observation suggests that the majority of 5‐FU in the matrix is in an amorphous state. [ 45 ] Comparing the XRD of HPMC and GO with that of composite, the characteristic peak of HPMC (22.9°) broad and distinct peaks of GO (8.99 and 44.4°) disappeared. [ 44 ]…”

“…This observation suggests that the majority of 5-FU in the matrix is in an amorphous state. [45] Comparing the XRD of HPMC and GO with that of composite, the characteristic peak of HPMC (22.9 • ) broad and distinct peaks of GO (8.99 and 44.4 • ) disappeared. [44] 3.1.3 Thermal analysis TGA is one of the main techniques used to evaluate the thermal properties of polymeric materials and nanocomposites.…”

Pre-Formulation Study on 5-Fluorouracil and Certain Lipids for Solid Lipid Nanoparticles Preparation

“…It was impossible to detect the separated melting peaks for compritol because of its complex structure during the heating scans due to its polymorphic nature [43]. When 5-FU was added to melted lipid, the drug was molecularly dispersed inside this lipid [44,45] leading to the presence of amorphous drug state [44,[46][47]. The hydrogen bond may be formed between the fluorine atom of 5-FU and the hydroxyl group of cholesterol [48].…”

An Overview of In Vitro Drug Release Methods for Drug-Eluting Stents

“…The use of shakers has been amongst the common methods of measuring the amount of drug release at the dynamic condition. For this purpose, a certain number of stents (usually one stent) to media are placed in the screwed-glass vials [73], tubes [74], or flasks [75], and then the test is performed at a certain agitation of the shaker. In most studies, the temperature intended for the experiment was kept constant at 37 • C by an incubator [72,76] or a water bath [73,77].…”

“…In most studies, the temperature intended for the experiment was kept constant at 37 • C by an incubator [72,76] or a water bath [73,77]. The agitation speed of shaker in studies considered in the range of 50 [78,79], 75 [80,81], 80 [75], 100 [73,76], 120 [77], 130 [82], 175 [74], 250 and 300 [83] rpm. Sampling in this method to check the amount of drug released has been one of the variable parameters, which consist of several methods.…”