Off-campus UNL users: To download campus access dissertations, please use the following link to log into our proxy server with your NU ID and password. When you are done browsing please remember to return to this page and log out.

Non-UNL users: Please talk to your librarian about requesting this dissertation through interlibrary loan.

Ingestible Capsules for Extended Retention and Systemic Delivery of Macromolecular Drugs in the Small Intestine

Sunandita Sarker, University of Nebraska - Lincoln

Abstract

Macromolecular drugs are relatively large and complex molecules compared with conventional synthetic drugs. An orally administered macromolecule may frequently become inactive or less potent as it may be hydrolyzed or degraded enzymatically in the GI tract before reaching its targeted location. Thus, macromolecule therapeutics typically require parenteral delivery, which includes intravenous (IV) and intramuscular (IM) delivery in hospitals, or subcutaneous (SC) injections at the patient's home. Injections are challenging to use in a long-acting continuous drug input system outside of the hospital and cause needle fear, and potentially treatment nonadherence. Ingestible or swallowable capsule devices can be utilized for long-term systemic drug delivery.Here, I present ingestible capsule devices for the systemic delivery of macromolecule drugs. First, a tissue attachment mechanism (TAM) for drug delivery in the small intestine was developed and optimized. A fractional factorial approach was used in vivo to identify and optimize factors that most influence attachment and an attachment success rate of 92% was achieved. Optimal TAMs were surgically placed in healthy swine animal models to determine the attachment duration which was found to be 32.2±9.4 hours. Next, the optimized TAM was used to develop an oral drug delivery device called the swallowable capsule for intestinal drug delivery (SCIDD) for the systemic delivery of physically and chemically unaltered biological drugs. After validating the subcomponents of the SCIDD, the assembled SCIDD was further tested both ex vivo and in vivo to characterize the action sequence. During ex vivo testing, 9 out of 12 SCIDDs performed all the functions correctly, while during in vivo testing, 12 out of 17 SCIDDs did. This device was also used in a separate drug delivery study and showed successful systemic drug delivery. Finally, an alternative design concept called the ‘soft stent’ was proposed to incorporate drug-loaded microneedles, mucoadhesive patches, or microdevices. The novel device showed promise in extended retention in the GI tract and successful contact, but proof of feasibility for systemic drug delivery is pending.

Subject Area

Mechanical engineering|Biomedical engineering|Pharmaceutical sciences|Robotics|Molecular biology

Recommended Citation

Sarker, Sunandita, "Ingestible Capsules for Extended Retention and Systemic Delivery of Macromolecular Drugs in the Small Intestine" (2021). ETD collection for University of Nebraska-Lincoln. AAI28714552.
https://digitalcommons.unl.edu/dissertations/AAI28714552

Share

COinS