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http://hdl.handle.net/11375/27819
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DC Field | Value | Language |
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dc.contributor.advisor | Wylie, Ryan | - |
dc.contributor.author | Zhang, Jiawei | - |
dc.date.accessioned | 2022-09-20T23:25:47Z | - |
dc.date.available | 2022-09-20T23:25:47Z | - |
dc.date.issued | 2022-11 | - |
dc.identifier.uri | http://hdl.handle.net/11375/27819 | - |
dc.description.abstract | Due to transport barriers and biological responses, repeated local injections are often required to achieve efficacy for protein-based therapeutics and vaccines. Strategies to achieve timed burst releases of proteins with a single injection are being developed to avoid the need for multiple injections, especially for high-risk injections or the treatment of remote populations. Herein, we report the first hydrogel platform that tunes two burst releases of a therapeutic antibody, bevacizumab, by combining an iminoboronate affinity release system with controlled hydrogel hydrolysis. The first burst release is controlled by the protein-iminoboronate reversible covalent interaction, where iminoboronate is immobilized to the polymer network, and can be tuned by (1) using a protein modified with oxyamine moieties to enhance complex formation, and (2) the inclusion of fructose, which decreases the strength of the protein-iminoboronate interaction. Protein release from hydrogels with affinity-controlled release mechanisms, which is similar to the reversible protein-iminoboronate interaction, often plateaus, which reserves protein for the second burst release. The timing of the second burst release, which comprises of terminating protein after the initial burst, is then controlled by the hydrolytic crosslink, which occurred ~3-4 weeks after initial hydrogel formation. Hydrogel degradation rates can be further tuned by altering hydrolysis kinetics. Therefore, affinity release in combination with controlled degradation allows for the construction of hydrogel platforms to achieve two burst releases from a single injection. | en_US |
dc.language.iso | en | en_US |
dc.title | Combining reversible interactions and controlled degradation for hydrogel-only pulsatile protein release | en_US |
dc.type | Thesis | en_US |
dc.contributor.department | Chemistry and Chemical Biology | en_US |
dc.description.degreetype | Thesis | en_US |
dc.description.degree | Master of Science (MSc) | en_US |
Appears in Collections: | Open Access Dissertations and Theses |
Files in This Item:
File | Description | Size | Format | |
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Zhang_Jiawei_2022September_MSc.pdf | 2.6 MB | Adobe PDF | View/Open |
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