Engineering Medical Devices to Improve Oral Delivery of Biopharmaceuticals

The dynamic mechanics of the gastrointestinal (GI) tract, including gut contractions, variable pH, and degradative enzymes, significantly challenge the development of oral delivery systems for biologic drugs by compromising their reliable delivery and therapeutic efficacy. While recent advances in oral delivery systems offer improved absorption through tissue penetration, their clinical translation remains tenuous due to the uncertainty of actuation-based delivery in variable environments and inherent design complexity. Inspired by the compression-based toxin delivery system of the stonefish, we developed a simple oral delivery device that harnesses GI mechanics to reliably actuate and systemically deliver biologic drugs. By synchronizing device actuation with gut contractions, the device and tissue work in tandem to ensure the complete transfer of a loaded therapeutic from the device to the tissue, bypassing physical and biochemical barriers and maximizing absorption. Through ex vivo and in silico experiments, we engineered the geometry of the device to achieve safe and targeted injections in the gut. An ex vivo electromechanical simulation model revealed the effectiveness of gut contractions for device actuation, and extensive in vivo experiments involving minipigs demonstrated comparable biologic drug delivery efficacy to subcutaneous injection. Harnessing the dynamic mechanics of the GI tract to improve oral delivery could transform drug administration and significantly enhance the lives of many patients.

Name thesis:degree_name

Doctoral

Department dc:contributor.department

Massachusetts Institute of Technology. Department of Biological Engineering

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2024

Author dc:creator

• Sharma, Shonit Nair

Advisors dc:contributor.advisor

• Karp, Jeffrey M.
• Lee, Yuhan
• Ribbeck, Katharina

Statement dc:rights

• In Copyright - Educational Use Permitted
• Copyright retained by author(s)

Licence dc:rights.uri

• https://rightsstatements.org/page/InC-EDU/1.0/

Handle dc:identifier.uri

https://hdl.handle.net/1721.1/157196

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/157196