Developing manufacturing methods for a lymph node-targeted cancer drug delivery vehicle

• Dylan Ngo, Human Physiology, University of Delaware

• Jason Gleghorn, Biomedical Engineering, University of Delaware

Dylan T. Ngo¹, Michael J. Donzanti², Jason P. Gleghorn²

Departments of Kinesiology and Applied Physiology¹ and Biomedical Engineering², University of Delaware, Newark DE 19716

A significant barrier to treating metastatic cancer or lymphoma is poor drug penetration into the lymph node (LN). The parenchymal spaces of the LN, called lobules, provide a safe haven for tumor cells, significantly reducing chances of patient survival. As tumor cells persist in the lymph node, distant sites are primed for further metastasis and immune tolerance is promoted. Thus, there is a dire need for the production of a more efficacious delivery vehicle for targeted, local chemotherapeutic delivery to the LN lobule. Previous research efforts have aimed to develop synthetic, nanoparticle-based drug vehicles for targeted drug delivery. These vehicles act as a shield to prevent drug degradation, control drug release before arrival at target tissue, and enhance drug retention compared to free delivered drugs. However, many of these technologies are cleared rapidly from the blood and issues with transport into the LN persist. Recently our lab has developed a promising therapeutic vehicle with the capability for drug loading and release and functional LN targeting. Our objective was to optimize the development of these drug delivery vehicles through surface modifications and characterize stability in vitro under physiological fluid flow conditions. We created a mimetic blood flow model that was validated as a screening tool for further stability testing of modified vehicles. Furthermore, we developed an efficient method to load doxorubicin, a chemotherapy drug, into our vehicles. This method has the potential to increase vehicle drug concentrations and improve drug release profiles. Our drug delivery approach would allow for significantly higher drug payload to the LN than current systems.