Dual Delivery of Gemcitabine and Paclitaxel by Wet-Spun Coaxial Fibers Induces Pancreatic Ductal Adenocarcinoma Cell Death, Reduces Tumor Volume, and Sensitizes Cells to Radiation

Authors

Samantha Wade, University of WollongongFollow
Zeliha Sahin, University of WollongongFollow
Ann-Katrin Piper, University of WollongongFollow
Sepehr Talebian, University of WollongongFollow
Morteza Aghmesheh, University of WollongongFollow
Javad Foroughi, University of WollongongFollow
Gordon G. Wallace, University of WollongongFollow
Simon E. Moulton, Swinburne University of Technology, University of WollongongFollow
Kara L. Vine, University of WollongongFollow

RIS ID

145748

Publication Details

Wade, S., Sahin, Z., Piper, A., Talebian, S., Aghmesheh, M., Foroughi, J., Wallace, G., Moulton, S. & Perrow, K. (2020). Dual Delivery of Gemcitabine and Paclitaxel by Wet-Spun Coaxial Fibers Induces Pancreatic Ductal Adenocarcinoma Cell Death, Reduces Tumor Volume, and Sensitizes Cells to Radiation. Advanced Healthcare Materials,

Abstract

© 2020 Wiley-VCH GmbH Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis, with surgical resection of the tumor in conjunction with systemic chemotherapy the only potential curative therapy. Up to 80% of diagnosed cases are deemed unresectable, prompting the need for alternative treatment approaches. Herein, coaxial polymeric fibers loaded with two chemotherapeutic agents, gemcitabine (Gem) and paclitaxel (Ptx), are fabricated to investigate the effect of local drug delivery on PDAC cell growth in vitro and in vivo. A wet-spinning fabrication method to form a coaxial fiber with a polycaprolactone shell and alginate core loaded with Ptx and Gem, respectively, is used. In vitro, Gem+Ptx fibers display significant cytotoxicity as well as radiosensitizing properties toward PDAC cell lines greater than the equivalent free drugs, which may be attributed to a radiosensitizing effect of the polymers. In vivo studies assessing Gem+Ptx fiber efficacy found that Gem+Ptx fibers reduce tumor volume in a xenograft mouse model of PDAC. Importantly, no difference in mouse weight, circulating cytokines, or liver function is observed in mice treated with Gem+Ptx fibers compared to the empty fiber controls confirming the safety of the implant approach. With further development, Gem+Ptx fibers can improve the treatment of unresectable PDAC in the future.