Controlled focal drug delivery by endovascular bioresorbable composite implants

Project Summary/Abstract Focal disease processes affect a specific organ, or part of an organ. Examples include primary tumors, inflammatory bowel disease, focal epilepsy, post-surgical pain, embolisms. The mainstay of medical management of these disease processes is drug treatment. However, the vast majority of our drug treatments of focal disease processes lack spatial targeting. For example, oral or intravenous drug treatments will deliver drug to the affected region; however, they will also expose all other organs to therapeutic drug levels. This systemic, off-target drug exposure causes severe, lethal side effects which limits our use of these medications in treating disease. To limit off-target side effects, there is significant interest in developing spatially targeted, focal drug delivery technologies. While some technologies have had important clinical impact, focal drug delivery has not yet achieved widespread success. We have developed intra- arterial drug-eluting bioresorbable composite implants that can reduce off-target drug exposure by 40-fold. For many drug treatments, this would effectively eliminate off-target side effects. Our implants are designed according to the four following criteria: (1) maximize drug storage and elution, (2) minimize disruptions to blood flow, (3) biocompatible for clinical use, and (4) biodegradable with tunable absorption rate when no longer needed. Moreover, this is a platform technology for delivery of a wide range of drugs, which can be used to treat an array of disease processes. Through this award, we intend to demonstrate the platform potential of our technology, by focally delivering two different drugs to two different organs. Additional analyses will assess for safety and efficacy of our intervention. If successful, the data obtained from this award would strongly motivate the next steps of product development for pre-clinical trials.