(L-444) Local iontophoretic drug delivery into in vitro tumor model

Introduction:: Current standard of care for locally advanced pancreatic cancer is systemic chemotherapy. Unfortunately, locally advanced pancreatic cancer remains lethal, with a 5 year survival rate of 11%. Major contributing factors to such low survival rates in pancreatic cancer are off-target toxicity and limited chemotherapy delivery into the tumor. In order to improve the treatment of pancreatic cancer we have designed an innovative device system for localized iontophoretic delivery of chemotherapeutic agents into tumors. Iontophoretic delivery uses an electric field to drive drugs into tissues to overcome diffusion barriers. Our previous in vivo work has shown that iontophoretic delivery of gemcitabine led to significantly higher intratumoral drug concentrations with lower systemic effects and tumor shrinkage in mouse xenograft pancreatic cancer models.

Materials and Methods:: To further understand our preclinical in vivo work testing local delivery of gemcitabine in pancreatic cancer, we aimed to develop a predictive in vitro model to test iontophoretic drug delivery in biologically relevant tumor models. Using bioprinting, we produced hydrogel scaffolds embedded with pancreatic cancer cell spheroids as an in vitro tumor model. We then developed a device to iontophoretically deliver chemotherapeutic agents across the in vitro model using an external power control. In vitro tumor hydrogel models were gemcitabine treated with and without iontophoresis.

Results, Conclusions, and Discussions::

Using a PrestoBlue viability readout, our preliminary results show that embedded pancreatic cancer cell spheroids treated with gemcitabine iontophoretically were less viable than spheroids treated with gemcitabine without iontophoresis. Our findings suggest that local iontophoretic delivery is a promising approach for pancreatic cancer treatment and that our in vitro hydrogel model correlates with in vivo preclinical work. Therefore, this work validates the use of our novel hydrogel model for evaluating additional cancer and chemotherapy combinations that would benefit from iontophoretic drug delivery.

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References (Optional): : Byrne, J. D., Jajja, M. R., O'Neill, A. T., Bickford, L. R., Keeler, A. W., Hyder, N., Wagner, K., Deal, A., Little, R. E., Moffitt, R. A., Stack, C., Nelson, M., Brooks, C. R., Lee, W., Luft, J. C., Napier, M. E., Darr, D., Anders, C. K., Stack, R., Tepper, J. E., … DeSimone, J. M. (2015). Local iontophoretic administration of cytotoxic therapies to solid tumors. Science translational medicine, 7(273), 273ra14. https://doi.org/10.1126/scitranslmed.3009951