Application of advanced structures in localised delivery of chemotherapy to pancreatic cancer: Proof of Concept

Research Seminar – 11 November 2014 : Application of advanced structures in localised delivery of chemotherapy to
Pancreatic Cancer: Proof of Concept
Presenters: Dr Mori Aghmesheh, A/Prof Simon Moulton, Dr Kara Perrow

The overall aim of this project is to develop and test novel, implantable three-dimensional (3D) drug-loaded polymeric nanofibers for the treatment of pancreatic cancer. This project will, through exploration and discovery of the appropriate material combinations, optimise drug release properties (kinetics) to be effective against pancreatic cancer cell lines in vitro. This is a timely and significant project considering medicinal nanotechnology (i.e. the integration of nanomaterials into therapeutics) is a newly emerging field and has already revolutionised the treatment of cancer. For example, nanocarriers synthesised from organic and inorganic materials (e.g. micelles, carbon nanotubes, dendrimers, quantum dots and nanofibers) have shown great potential by enhancing the performance of medicines and reducing systemic side effects in order to gain therapeutic efficiency. In particular, electrospun nanofibers (fibers with diameters less than 1 micrometer that are formed using the spinning process have the potential to be used as antitumour drug carriers because the delivery of the drugs can be easily set to the targeted area, and the drug release profile from the nanofibers can be highly controlled by modulating the fiber morphology, porosity and composition. They offer great potential as novel scaffolds to deliver drugs with sustained release profiles and ultimately long-term antitumour activity for anticancer therapy. This is the first time the electrospinning process will be used to load the anticancer drug Abraxane and Gemcitabine into biocompatible polymeric nanofibers with the view to form implantable structures for the treatment of pancreatic cancer.

The innovative aspect of this project is the fabrication of 3D Abraxane loaded polymer nanofibers that can be i) used to coat biliary stent when the cancer is located in the head of the pancreas or alternatively ii) surgically implanted directly at the site of the primary pancreatic cancer when it is in the body or tail of the pancreas, allowing for localised drug delivery. The ability to administer an anticancer drug directly at the site of the tumour holds great promise in avoiding many of the undesirable whole body effects normally associated with systemic chemotherapy.

This is anticipated to result in the ability to deliver a higher dose of anticancer drug. In addition, since the drug is delivered directly at the site of the tumour the total amount of drug acting on the tumour remains in the therapeutic range longer, therefore greatly increasing the efficacy of treatment. It is important to note that while the structures to be developed in this project are targeted towards the treatment of pancreatic cancer, the processes developed to form 3D drug loaded polymer nanofibers are applicable to any cancer requiring chemotherapeutic intervention. The project involves a direct collaboration between clinician from cancer services at ISLHD and researchers from two other institutions at two separate facilities; Associate Professor Simon Moulton from IPRI and Dr. Kara Perrow from IHMRI. Outcomes from this proof of concept study will advance our understanding of the use of novel material architectures to deliver anticancer drugs to cancer cells. It is anticipated that these studies will lead to the future development of a safe and effective delivery system designed to combat different type of cancer for which currently there is minimal chance of cure. This technology may also be applied to a broader range of cancers, for example malignant brain tumours, where sustained local release from an implantable delivery system would be an advantage.



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