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Access Type
WSU Access
Date of Award
January 2025
Degree Type
Dissertation
Degree Name
Ph.D.
Department
Chemical Engineering and Materials Science
First Advisor
Zhiqiang Cao
Abstract
The treatment of Type 1 diabetes (T1D) presents significant challenges, as patients rely entirely on external insulin to regulate blood glucose levels. Conventional insulin therapies, often require frequent administration and carry a substantial risk of hypoglycemia. Current insulin infusion pump system also needs frequent calculation and input of estimated meal calories. In contrast, glucose-responsive insulin (GRI) systems offer a promising solution by mimicking the body's natural insulin regulation, releasing insulin dynamically in response to glucose levels. This dissertation introduces a novel GRI delivery system based on a copolymer containing human recombinant insulin. At low blood glucose levels, the copolymer insulin remains within the formulation, minimizing systemic glycemic effects. At high blood glucose levels, the copolymer insulin is triggered to release from the formulation, enabling glucose-responsive insulin release and effective glycemic control. This dissertation focused on three GRI formulations. An implantable GRI formulation was developed to target long-term diabetes correction, demonstrating effective glucose responsiveness in both small and large animal models. Additionally, an injectable GRI formulation for subcutaneous administration was developed, exhibiting improved efficacy, ease of use, and dose potency, as validated in diabetic mice and Göttingen minipigs. Finally, a pilot oral GRI capsule prototype was developed to overcome gastrointestinal barriers. This oral formulation prototype demonstrated glucose responsiveness and stable pharmacokinetics in diabetic rats, offering a potential non-invasive alternative to traditional insulin delivery methods. A key innovation of this GRI system lies in the tunability of the copolymer insulin’s glucose responsiveness. This enables precise insulin release tailored to individual patient needs, offering a path toward personalized diabetes management. Together, these advancements represent a significant step forward in the development of safer, more effective, and patient-friendly insulin therapies for T1D.
Recommended Citation
Shi, Yuanjie, "Glucose-Responsive Insulin For The Treatment Of Diabetes" (2025). Wayne State University Dissertations. 4169.
https://digitalcommons.wayne.edu/oa_dissertations/4169