Abstract
For several decades, self-expanding metal stents (SEMSs) have shown significant clinical success in the palliation of obstructive metastatic oesophageal cancer. However, these conventional oesophageal stents can suffer from stent blockage caused by malignant tumour cell growth. To overcome this challenge, there is growing interest in drug-releasing stents that, in addition to palliation, provide a sustained and localized release of anticancer drugs to minimise tumour growth. Therefore, in this study we prepared and evaluated an oesophageal stent-based drug delivery platform to provide the sustained release of docetaxel (DTX) for the treatment of oesophageal cancer-related obstructions. The DTX-loaded oesophageal stents were fabricated via dip-coating of bare nitinol stents with DTX-polyurethane (PU) solutions to provide PU coated stents with DTX loadings of 1.92 and 2.79% w/w. Mechanical testing of the DTX-PU coated stents revealed that an increase in the drug loading resulted in a reduction in the ultimate tensile strength, toughness and Young’s modulus. In vitro release studies showed a sustained release of DTX, with ~80–90% released over a period of 33 days. While the DTX-loaded stents exhibited good stability to gamma radiation sterilisation, UV sterilisation or accelerated storage at elevated temperatures (40 °C) resulted in significant DTX degradation. Cell proliferation, apoptosis and Western blotting assays revealed that the DTX released from the stents had comparable anticancer activity to pure DTX against oesophageal cancer cells (KYSE-30). This research demonstrates that the dip-coating technique can be considered as a promising approach for the fabrication of drug-eluting stents (DESs) for oesophageal cancer treatment.
Highlights
Multiple dip-coating cycles were implemented to prepare multiple-layer coatings, with an increase in the layers correlating to an increase in the burst release, the overall drug release plateaued at ~70–80% by day 11 regardless of the number of layers. Whilst these studies have been performed on coronary drug-eluting stents (DESs), no investigations employing dip-coating have been reported for the fabrication of oesophageal stents, we have recently demonstrated the potential of this approach for the preparation of 5-fluorouracil-loaded drug-eluting colonic stents [27]
To combine the mechanical support of oesophageal stents and the longer-term benefit of localized, sustained release of chemotherapeutics, we aimed to prepare and evaluate an oesophageal stent-based drug delivery platform to provide the sustained release of DTX
These results demonstrate that the DTX released from the stents induced an obvious inhibitory effect on the proliferation of KYSE30 cells, indicating that the DES, as a controlled-releasing system, possessed similar antitumour effects to the pure
Summary
Oesophageal cancer is the seventh most common cancer in men and the thirteenth most common cancer in women, with more than 500,000 new cases reported in 2018 [1]. Oesophageal cancer has two distinct histological subtypes, which carry varying risk factors, contributing to the widespread incidence rates of the disease [2]. The vast majority of cases are related to squamous cell carcinoma, with has a high incidence rate in developing countries [3]. The rate of adenocarcinomas is dramatically increasing with a greater burden in high-income countries [4]. Depending on the stage of the disease, several treatments are currently used including surgery, chemotherapy, radiotherapy, Pharmaceuticals 2021, 14, 311.
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