(56h) Precision Nanomedicines to Deliver Kinase Inhibitors to the Tumor Microenvironment
AIChE Annual Meeting
2017 Annual Meeting
Nanoscale Science and Engineering Forum
Bionanotechnology for Gene and Drug Delivery II
Monday, October 30, 2017 - 10:06am to 10:24am
We developed and validated a nanoscale formulation technology to incorporate high drug loadings of kinase inhibitors. The resulting nanoparticles obviate dose-limiting toxicities of kinase inhibitors and thereby improve therapeutic index in solid tumors. We developed a polysaccharide-based nanoformulation platform which targets kinase inhibitors to P-selectin on tumor vasculature. P-selectin is expressed endogenously in certain tumors, but it can be greatly induced by radiation therapy. Our data shows striking efficacy with MEK and PI3K inhibitors and the abrogation of dose-limiting toxicities, such as skin rash and hyperglycemia, to greatly improve therapeutic index. Moreover, measurements of tumor tissue show prolonged inhibition of downstream effectors in the signaling pathways, constituting a significant modulation of drug pharmacodynamics.