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.
Highlights
Pharmaceutical Innovation and Development (PIDG) Group, Clinical and Health Sciences, University of ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Clinical and Health Sciences, Drug Discovery and Development Group, Clinical and Health Sciences, University of South
The poly(ethylene-co-vinyl acetate) (PEVA) solution was dip-coated onto the stents, air dried for 24 h, and weighed to determine the mass of the topcoat
While the basecoat acts as the drug reservoir, the topcoat was intended to mediate the diffusion and release of the highly hydrophilic 5FU
Summary
Pharmaceutical Innovation and Development (PIDG) Group, Clinical and Health Sciences, University of ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Clinical and Health Sciences, Drug Discovery and Development Group, Clinical and Health Sciences, University of South. 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. 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. 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. Colorectal cancer (CRC) remains the second leading cause of cancer deaths and the third most commonly diagnosed cancer globally. More than 70% of patients already have advanced CRC at diagnosis, and only half of these patients are suitable candidates for curative one-stage
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