Ingestible Devices and Technologies for Controlled and Localized Gastrointestinal Drug Delivery

Abstract

The gastrointestinal (GI) tract is an integral organ system in the human body that acts as a gateway for the absorption of nutrients and drugs into the body. The GI tract is also frequently plagued with a variety of diseases, like IBD or cancer, that impact quality of life for patients and are increasingly common. Oral drug delivery is preferred by patients, leading to better compliance and outcomes; however, effective storage, delivery, and transport across biological barriers presents challenges for many of the most useful drugs. This work shows the development and demonstration of ingestible technologies for controlled drug carriage and release in the GI tract. The approaches used here leverage a microsystems-based technological approach toward improving drug therapies, representing the potential of such hybrid techniques for drug delivery and other biomedical applications. This dissertation addresses the development of (1) actuation technologies for ingestible devices, (2) the ingestible devices to package and power the actuators, and (3) the attachments to carry and deliver drugs from the actuation capsule. Specifically, a thermomechanical actuation was developed for actuation from ingestible devices. The actuator comprised a spring component to store elastic potential energy for actuation and a microfabricated Au heater to melt glue that holds the spring in compression. Using the heating element as a trigger, a cantilever actuator module was also developed to deploy radially from the capsule for drug delivery. The cantilever actuator showed excellent control over force application and resilience to prolonged compression, with the ability to apply >1 N of force and remain elastic after 60 or more days of compression. To facilitate implementation of the actuators, a magnetic triggering capsule was developed using a button cell battery and magnetic reed switch in series with the cantilever actuator. Deployment of the cantilever actuator within 2.9 seconds was achieved using this magnetic switching capsule. As a step toward clinical implementation, the magnetic deployment capsule was miniaturized to a =8.8 mm and L=20.7 mm, smaller than a 000-pill capsule commonly used for oral medications. Moreover, a proof-of-concept device was developed for closed-loop deployment of the cantilever actuator using embedded electronics and a bioimpedance sensor on the capsule surface. Finally, a versatile drug injection system was created using a hybrid fabrication process merging vat photo-polymerization (VPP) 3D printing with direct laser writing (DLW) to achieve large drug loading volumes with sharp and versatile microneedles. The drug injectors enable extended control over the delivery rate via material and geometry modifications that impact the convective and diffusional release rate from the injectors. Injection half-lives of between 4 seconds and 115 days were proven to be attainable through simulation and benchtop testing. The demonstrated success of the capsular actuation technologies and injectors paves a pathway for future integration and implementation of such devices for localized drug delivery in the clinic.