Drug-Loaded, Polyurethane Coated Nitinol Stents for the Controlled Release of Docetaxel for the Treatment of Oesophageal Cancer

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.

A Study of PLA Thin Film on SS 316L Coronary Stents Using a Dip Coating Technique

“…The observed porosity depends on the mechanism of solvent evaporation during the drying process [ 59 ]. Fouladian et al (2021) mentioned that cavities appear during solvent evaporation due to water condensation as the surface cools, leading to respiration and the formation of defined structures on the surface [ 31 ]. The increase in pore depth can be correlated with sample viscosity as PLA concentration increases.…”

Utilizing 4D Printing to Design Smart Gastroretentive, Esophageal, and Intravesical Drug Delivery Systems

“…[22] Recently, nitinol has gained great interest in drug delivery field as a shape memory alloy to fabricate drug releasing stents (e.g., through coating with a drug loaded polymeric matrix) to target various body organs. [25][26][27][28] In addition to the stents, the use of nitinol as a shape memory material in combination with other smart materials to fabricate drug delivery devices such as esophageal device has been reported. [29] Accordingly, shape memory alloys can be regarded as a potential class of smart materials for drug delivery applications.…”

Current status and advances in esophageal drug delivery technology: influence of physiological, pathophysiological and pharmaceutical factors

“…Many esophageal self-expanding stents have been investigated for the delivery of chemotherapeutic agents for the treatment of esophageal cancer (e.g. docetaxel (Huang et al., 2015 ; Shaikh et al., 2015 ; Fouladian et al., 2021 ), paclitaxel (Zhang et al., 2017b ; Jin et al., 2018 ; Xia et al., 2019 ), 5-fluorouracil (Guo et al., 2010 ; Liu et al., 2015 ; Wang et al., 2015 ), radioactive seeds (e.g. Iodine 125 (Guo et al., 2008 ,Zhang et al., 2021 )), and cytotoxic polymers (e.g.…”