Jesse Xu1,2, Hui Xin Ong1,2, Daniela Traini1,2, Jonathan Williamson3,4, Michael Byrom5, Larissa Gomes Dos Reis1, Paul M Young1,2. 1. Respiratory Technology Group, Woolcock Institute of Medical Research , Sydney, Australia. 2. Discipline of Pharmacology, Faculty of Medicine and Health, University of Sydney , Sydney, Australia. 3. South West Clinical School, The University of New South Wales , Sydney, Australia. 4. MQ Health, Respiratory and Sleep, Macquarie University , Sydney, Australia. 5. RPA Institute of Academic Surgery , Sydney, Australia.
Abstract
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 compared in vitro at 37°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 (R2 > 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.
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 compared in vitro at 37°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 (R2 > 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.
Entities:
Keywords:
Airway stents; central airway obstruction; drug release; granulation tissue; lung cancer; paclitaxel; personalized; stenting; tracheobronchomalacia