TY - JOUR
T1 - Paclitaxel-eluting silicone airway stent for preventing granulation tissue growth and lung cancer relapse in central airway pathologies
AU - Xu, Jesse
AU - Ong, Hui Xin
AU - Traini, Daniela
AU - Williamson, Jonathan
AU - Byrom, Michael
AU - Gomes Dos Reis, Larissa
AU - Young, Paul M.
PY - 2020/11/1
Y1 - 2020/11/1
N2 - 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.
AB - 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.
KW - Airway stents
KW - central airway obstruction
KW - drug release
KW - granulation tissue
KW - lung cancer
KW - paclitaxel
KW - personalized
KW - stenting
KW - tracheobronchomalacia
UR - http://www.scopus.com/inward/record.url?scp=85090017299&partnerID=8YFLogxK
U2 - 10.1080/17425247.2020.1811224
DO - 10.1080/17425247.2020.1811224
M3 - Article
C2 - 32815403
AN - SCOPUS:85090017299
SN - 1742-5247
VL - 17
SP - 1631
EP - 1645
JO - Expert Opinion on Drug Delivery
JF - Expert Opinion on Drug Delivery
IS - 11
ER -