Ultrasound Controlled Drug Delivery by Acoustically Switchable Hydrogels

Author: Abundo, Maria Paulene Bernal

Year: 2023

Degree: Dissertation (Ph.D.)

Advisor: Shapiro, Mikhail G.

Committee Members: Brady, John F.; Daraio, Chiara; Gao, Wei; Shapiro, Mikhail G.

Option: Chemical Engineering

DOI: 10.7907/5rr6-q625

Abstract

Not only is ultrasound widely used as a diagnostic imaging modality, it can also be focused into deep tissues to perform non-invasive actuation of cells, implants and delivery vehicles and other biological targets. With the addition of gas vesicles (GV), generic hydrogel materials gain the ability to communicate with ultrasound, equipping them with in vivo tracking, targeting and actuation capabilities to safely transport biomolecular cargo. This is possible as GVs function simultaneously as ultrasound contrast agents and steric blockers that can be "erased" by an increase in ultrasound pressure to trigger a rapid outflow diffusion of the payload from within the material. We evaluate this concept through in vitro measurements of ultrasound-modulated diffusion and drug release and targeted in vivo release in the lower gastrointestinal tract. Then we demonstrate the use of orally administered hydrogel particles to deliver etanercept in the duodenum to treat gastrointestinal inflammation in a rat model of colitis. Finally, we explore new directions and applications of GV-hydrogel systems, showcasing their potential for deployment in a wide range of biomedical applications.

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