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Access Type

WSU Access

Date of Award

January 2021

Degree Type


Degree Name



Chemical Engineering and Materials Science

First Advisor

Zhiqiang Cao


Oral delivery of protein drugs is considered a life-changing solution for patients who require regular needle injections. However, clinical translation has been hampered by inefficient penetration of drugs through the intestinal mucus and epithelial cell layer, leading to low absorption and bioavailability, and safety concerns owing to tight junction openings. Here we report a zwitterionic micelle platform featuring a virus-mimetic zwitterionic surface, a betaine side chain, and an ultralow critical micelle concentration, enabling drug penetration through the mucus and efficient transporter-mediated epithelial absorption without the need for tight junction opening. This micelle platform was used to fabricate a prototype oral insulin formulation by encapsulating a freeze-dried powder of zwitterionic micelle insulin into an enteric-coated capsule. The biocompatible oral insulin formulation shows a high oral bioavailability of >40%, offers the possibility to fine-tune insulin acting profiles, and provides long-term safety, enabling the oral delivery of protein drugs. The use of zwitterionic micelle was further extended for oral delivery of exenatide, a glucagon-like peptide receptor 1 agonist (GLP-1RA). High pharmacological activity (>40%) was achieved on diabetic mice and minipig models, meanwhile, nausea, a common side effect associated with regular subcutaneous exenatide treatment, was significantly reduced. This work overall extends the applicability of zwitterionic materials for oral delivery of proteins/peptides or other biological drugs.

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