Engineering drug-eluting coatings to design next generation devices for locally treat pancreatic cancer.

摘要

The results constitute a proof-of-principle that effective engineering of coated devices can overcome multiple PDAC chemoresistance mechanisms by local delivery of conventional chemotherapeutic agent. This strategy opens the door for a new therapeutic paradigm of localized drug delivery to treat pancreatic cancer. By building an ad hoc mouse-sized paclitaxel-eluting device, we were able to show its safety and efficacy, and superiority to standard intravenous administration in a pancreatic orthotopic xenograft mouse model. Moreover, we developed a technique to computationally model the differences in drug delivery between I.V. and localized PED therapy, which provides a path to test a variety of novel agents for the platform device in silico before full development and utilization. Our approach addresses a major clinical problem and provides mechanistic insights to drive new devices to the clinic safely, effectively and rapidly.