Special Seminar: Controlled Drug Release and Refilling of Therapeutic Depots—Applications in Ischemia and Cancer

Yevgeny Brudno, Fellow, Wyss Institute

Friday, February 12, 2016, 3:30–4:30pm

Spanos Auditorium, Thayer School of Engineering

Drug-eluting polymer systems have proven useful in a variety of clinical settings, including preventing restenosis with stenting, treating cancer and enhancing wound healing. These systems benefit from tunable drug release kinetics, continuous drug release, and local delivery, which together provide spatiotemporal control over drug availability and diminish drug toxicity. This seminar will describe advances in spatiotemporal control over growth factor presentation to enhance neovascularization, vessel maturation and vascular remodeling. The talk will also describe our efforts to overcome one major hurdle to widespread use of drug-eluting systems in vivo that they carry a finite depot of drug and require invasive procedures to refill. We demonstrate that implanted polymer depots can be modified to capture circulating drug refills, allowing for repeated refilling of the depots for local release. Bioorthogonal chemistry and nucleic acid-based methods for selective depot replenishment will be discussed. Repeated drug refilling and release improved outcomes in cancer models and allowed for selective drug homing in models of lower limb ischemia and osteomyelitis. Refillable drug delivery devices that enable repeated and spatiotemporally controlled drug release may have clinical applications in cancer therapy, wound healing, immunotherapy, and drug-eluting vascular grafts and stents.

About the Speaker

Yevgeny Brudno received his bachelor's degrees in chemistry and biophysics from the University of Pennsylvania in 2004 and a PhD in chemical biology from Harvard University in 2010. As a graduate student, he developed methods to rapidly synthesize and screen sequence-defined synthetic polymers for biological and medical application. This advance allows creating protein-like synthetic polymers and selecting for active versions from libraries of greater than 100 million members. As a post-doctoral scholar with professor David Mooney, Yevgeny developed therapeutic scaffolds with temporal control over release of growth factors and identified optimal presentation kinetics for four pro-angiogenic and pro-vascular maturation growth factors and showed that controlled release of these factors lead to improved vascularization, stromal cell recruitment and vascular remodeling. Yevgeny is currently a Wyss Institute Fellow, and is developing the first technology allowing for non-invasive replenishment of drug- and growth factor-releasing hydrogels and surfaces. This widely applicable method allows for repeated, local and controlled release of therapeutic factors in a wide range of diseases and tissue engineered constructs. Yevgeny has also been actively involved in commercializing the refillable depot technology for medical applications.

For more information, contact Jessica Widdicombe at jessica.c.widdicombe@dartmouth.edu.