Changing the treatment paradigm: Ex vivo assessment of gemcitabine-eluting degradable polymeric fibres for the treatment of pancreatic cancer

Abstract

Event Abstract Back to Event Changing the treatment paradigm: Ex vivo assessment of gemcitabine-eluting degradable polymeric fibres for the treatment of pancreatic cancer Simon Moulton1, 2, Amanda Zuzic1, Samantha Wade3, Javad Foroughi1, Morteza Aghmesheh4 and Kara Vine3 1 University of Wollongong, ARC Centre of Excellence for Electromaterials Sciences, Australia 2 Swinburne University of Technology, Faculty of Science, Engineering and Technology, Australia 3 University of Wollongong, Illawarra Health and Medical Research Institute, Australia 4 Illawarra Shoalhaven Local Area Health District, Illawarra Cancer Care Centre, Australia Pancreatic cancer (PC) has a dismal prognosis with a 5-year overall survival of only 1-4%. At first diagnosis, only 20% of PC patients present with primarily resectable (surgically removable) disease, and locally advanced, non-metastatic PC is observed in up to 30-40% of patients. Median overall survival (OS) of primarily resectable patients is 20–24 months, while survival is only 9–13 months in locally advanced PC. Studies suggest that up to 15% of PC patients die with locally advanced PC due to the non-resectable nature of the disease[1]. It is therefore clear that surgical resection is an absolute requirement for achieving long-term survival and/or cure of PC[2]. We hypothesise that the surgical implantation of a degradable drug-eluting polymeric structure, capable of locally administering the anticancer drug gemcitabine (current standard of care for PC) will achieve tumour control and convert non-resectable PC cases to resectable cases to improve overall survival. Therefore the aim of this study was to fabricate and characterise the physicochemical and in vitro biological properties of gemcitabine-loaded wet-spun polymeric fibres for the future development of an implantable drug delivery system capable of improving PC patient survival. Gemcitabine loaded polymeric fibres had a uniform surface area, were internally homogeneous and ranged from 50-120μm in diameter as determined by SEM. Mechanical testing revealed an increase in the young’s modulus when the concentration of gemcitabine was increased, indicating a slight loss in elasticity. Encapsulation efficiency of gemcitabine ranged from 60-90% depending on the type and percent composition of polymer used. The release profiles of gemcitabine loaded fibres displayed burst release, typical for these hydrogel fibres. Approximately 85% of the loaded drug was released in the first 8 hours followed by a sustained, slow release of drug over the next 72 hours. A time dependent inhibition of PANC-1 spheroid growth and decrease in cell viability was observed after incubation with gemcitabine loaded fibres but not control fibres. There was no significant difference in the inhibition of PANC-1 spheroid growth after incubation with 10 μM free gemcitabine or 10 μM equivalent Gemcitabine-loaded fibres indicating bioequivalence. Australian Institute of Innovative Materials; University of Wollongong Science, Medicine and Health Faculty; University of Wollongong Vice Chancellor’s Fellowship; Australian Research Council