Injectable Biomimetic Hydrogels Providing Prolonged Delivery of GLP-1 Analogues for Enhanced Diabetes Treatment
Abstract/Contents
- Abstract
- In the US, there are over 130 million people living with Type 2 diabetes (T2D), who suffer from impaired regulation of hepatic glucose production, which eventually leads to β-cell failure. While insulin treatments are often recommended, they are burdensome to appropriately dose and can lead to dangerous hypoglycemic events. In contrast, glucagon- like peptide-1 receptor agonists (GLP-1 RAs), which mimic an incretin hormone secreted following carbohydrate intake, stimulate insulin and block glucagon secretion in a glucose- dependent manner, thereby eliminating the risk of hypoglycemia. These treatments lower endogenous glucose production and drive expansion of insulin-secreting β-cells to restore the native ability of patients to regulate glycemia. Unfortunately, current GLP-1 RAs must be injected either daily (Liraglutide) or weekly (Semaglutide), which results in significant patient burden and poor patient compliance. An ideal GLP-1 RA drug would provide continuous therapy for upwards of four months from a single administration during each primary care visit, which is the frequency which T2D patients visit their physician. In this work, we leverage an injectable hydrogel depot technology to develop a long-acting GLP- 1 RA drug. We show that a single injection of hydrogel-based therapies prolongs GLP-1 RA exposure and significantly improves management of blood glucose and weight in a rat model of T2D when compared with daily injections of a leading drug molecule over 42 days. Overall, we anticipate this work demonstrates the potential of a GLP-1 RA depot to dramatically reduce the frequency of therapeutic interventions, significantly increasing patient quality of life.
Description
| Type of resource | text |
|---|---|
| Publication date | May 4, 2023 |
Creators/Contributors
| Author | Lu, Katie |
https://orcid.org/0000-0002-4546-6942
(unverified)
|
|---|---|---|
| Thesis advisor | Appel, Eric | |
| Thesis advisor | d'Aquino, Andrea | |
| Thesis advisor | Dixon, Scott | |
| Degree granting institution | Stanford University, Department of Biology |
Subjects
| Subject | Biology |
|---|---|
| Subject | Bioengineering |
| Subject | Type 2 diabetes |
| Subject | Diabetes |
| Subject | Materials science |
| Genre | Text |
| Genre | Thesis |
Bibliographic information
Access conditions
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 4.0 International license (CC BY-NC).
Preferred citation
- Preferred citation
- Lu, K. and Appel, E. (2024). Injectable Biomimetic Hydrogels Providing Prolonged Delivery of GLP-1 Analogues for Enhanced Diabetes Treatment. Stanford Digital Repository. Available at https://purl.stanford.edu/pk538cj9584. https://doi.org/10.25740/pk538cj9584.
Collection
Undergraduate Theses, Department of Biology, 2022-2023
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- Contact
- katielu@stanford.edu
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