Paclitaxel-eluting silicone airway stent for preventing granulation tissue growth and lung cancer relapse in central airway pathologies

摘要

Background Airway stents are used to treat obstructive central airway pathologies including palliation of lung cancer, but face challenges with granulation tissue growth. Paclitaxel is a chemotherapy drug that also suppresses growth of granulation tissue. Yet, side effects arise from administration with toxic solubilizers. By incorporating paclitaxel in silicone stents, delivery of paclitaxel can be localized, and side effects minimized. Methods Paclitaxel was incorporated into Liquid Silicone Rubber (LSR) containing polydimethylsiloxane, either as a powder or solution, prior to curing. Drug release study was comparedin vitroat 37 degrees C over 10 days. Drug release was quantified using HPLC, and bronchial cell lines were grown on LSR to investigate drug cytotoxicity, and expression of inflammatory markers, specifically interleukin-6 and interleukin-8. Results Release rate of paclitaxel incorporated into silicone rubber was consistent with the Korsmeyer and Weibull models (R-2 > 0.96). Paclitaxel exposure reduced IL-8 levels in cancer cell lines, whilst no cytotoxic effect was observed in all cell lines at treatment concentration levels (<= 0.1% (w/v) paclitaxel in silicone). Conclusions Incorporating paclitaxel into a silicone matrix for future use in a tracheobronchial stent was investigated. Drug release from silicone was observed and is a promising avenue for future treatments of central airway pathologies.