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MEMP - Thesis Defense - Christopher Lee

Monday, July 9, 2018 -- 10:00am

MIT Sloan School of Management, Arthur D. Little Building, E60-112 
30 Memorial Drive, Cambridge MA 02142

Local Drug Delivery for Relaxation of the Ureter

Human ureteral contraction and relaxation is implicated in common physiologic situations. The success or failure of kidney stone expulsion and the body’s pain response to ureteral stents placed during urologic surgery are affected significantly by ureteral contractions. The lifetime prevalence of kidney stones alone in the US is roughly 10% (of the entire population), and annual health incidence and healthcare costs exceed 2.5M cases and $5bn annually. Worldwide, an additional 1M ureteral stents are placed annually. The ability to decrease ureteral contractions has been shown to improve spontaneous stone passage rates and decrease ureteral stent pain. Several candidate oral medications have been tested but study outcomes are equivocal. Additionally, no oral therapy has been shown to be associated with substantial reproducible positive outcomes. 

There are currently no topical therapies available for ureteral relaxation. We hypothesize that greater ureteral relaxation can be achieved with local administration of vasodilators compared with current standard oral therapy. We report the discovery and development of a drugs and drug formulations that can be locally delivered to the ureter via an office-based approach. We screened representative drugs in vitro that can induce smooth muscle relaxation in the ureter and found potent hits. We verified the effect of the drugs ex vivo and then compounded our drug candidates into a clinically deployable formulation. We ultimately show that using an office-based approach, we can deliver high topical drug doses to induce greater ureteral relaxation using an in vivo porcine model. These results have the potential to create a new class of therapeutics, topical ureteral relaxants, for common ureter- and urology-related conditions.
Thesis Supervisor:
Michael J. Cima, PhD
David H. Koch Professor of Engineering, MIT

Thesis Committee Chair:
Robert S. Langer, ScD 
David H. Koch Institute Professor of Engineering, MIT

Thesis Reader:
Brian H. Eisner, MD
Assistant Professor of Surgery, HMS
Date and Time: 
Monday, July 9, 2018 - 10:00am to 12:00pm

MIT Sloan School of Management, Arthur D. Little Building, E60-112
30 Memorial Drive, Cambridge MA 02142