Supramolecular hydrogels for stability and long-term delivery of biotherapeutics
Abstract/Contents
- Abstract
- Biotherapeutics are an important category of pharmaceuticals, used to treat everything from diabetes to cancer to infectious disease. Unfortunately, biotherapeutics have unique challenges compared to other drug types when it comes to pharmaceutical formulation due to their complex, and often fragile, molecular structures. As a result, these drugs are prone to denaturation and aggregation, and in general exhibit poor stability in formulation. Further, these drugs also may not exhibit favorable pharmacokinetics, especially for treatments where the drug would be administered long-term and repeat dosing would be required to maintain therapeutic or prophylactic efficacy. My doctoral work has focused on leveraging materials science to develop biotherapeutic formulation and delivery technologies to enable new treatment approaches for a variety of target applications. In particular, I have been studying the application of injectable, supramolecular polymer-nanoparticle (PNP) hydrogels as both stabilizing excipients and drug delivery vehicles for biotherapeutic drugs. First, I will introduce the PNP hydrogel platform and a detailed protocol for how to formulate the material for different biotherapeutic delivery applications. Second, I will discuss how these hydrogels can be used to encapsulate biotherapeutics, such as insulin and monoclonal antibodies, and greatly improve their thermal stability, reducing the need for refrigerated transportation and storage. Then, I will describe our approach to engineering this supramolecular hydrogel platform as a subcutaneous drug delivery depot for sustained delivery of monoclonal antibodies for passive immunization. I have also incorporated pharmacokinetic (PK) modeling to interpret the results of in vivo studies as well as to inform the design of future biomaterials for drug delivery applications. Lastly, I describe collaborative work developing a novel amphiphilic copolymer as a "drop-in" excipient to stabilize high-concentration antibody formulations. Overall, this work illustrates both the utility of materials science in addressing pharmaceutical formulation challenges and point towards important considerations for biomaterials design for drug delivery.
Description
| Type of resource | text |
|---|---|
| Form | electronic resource; remote; computer; online resource |
| Extent | 1 online resource. |
| Place | California |
| Place | [Stanford, California] |
| Publisher | [Stanford University] |
| Copyright date | 2022; ©2022 |
| Publication date | 2022; 2022 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Kasse, Catherine Marie |
|---|---|
| Degree supervisor | Appel, Eric (Eric Andrew) |
| Thesis advisor | Appel, Eric (Eric Andrew) |
| Thesis advisor | DeSimone, Joseph M |
| Thesis advisor | Kim, Peter, 1958- |
| Degree committee member | DeSimone, Joseph M |
| Degree committee member | Kim, Peter, 1958- |
| Associated with | Stanford University, Department of Materials Science and Engineering |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Catherine M. Kasse. |
|---|---|
| Note | Submitted to the Department of Materials Science and Engineering. |
| Thesis | Thesis Ph.D. Stanford University 2022. |
| Location | https://purl.stanford.edu/jr687hz0138 |
Access conditions
- Copyright
- © 2022 by Catherine Marie Kasse
- License
- This work is licensed under a Creative Commons Attribution Non Commercial No Derivatives 3.0 Unported license (CC BY-NC-ND).
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