Dissertation
Synthesis and Performance of Stimuli-Responsive Polymeric Biomaterials for Immunological and Therapeutic Application
Washington State University
Doctor of Philosophy (PhD), Washington State University
2023
DOI:
https://doi.org/10.7273/000006341
Abstract
Macromolecular platforms for delivery of therapeutics have long been a desirable strategy for treatment of various pathologies. While improving the bioavailability and efficacy of certain therapeutics, these methods have historically been limited due to systemic toxicity or irregular and uncontrolled release profiles. This has led to substantial interest in the design and application of biomaterials which can modulate activity or exhibit precise delivery of therapeutic agents to the disease site in response to certain physiochemical triggers. Such “stimuli-responsive biomaterials” can respond to their environment to allow for specified treatment tailored for spatial and temporal accuracy. This dissertation discusses the development of various stimuli-responsive platforms for therapeutic treatment including temperature responsive polymeric vaccine adjuvants and pH-responsive copolymers for controlled payload release. This is achieved by incorporating rationally designed therapeutic agents or chemical functionalities into polymeric architectures with comonomers to yield macromolecular biomaterials which can be tailored toward a desired clinical benefit. This modular approach allows for a variety of therapeutic strategies together with the performance benefits of macromolecular scaffolds towards the chosen application. Specifically, the development of novel thermoresponsive vaccine adjuvants demonstrates modulation of proinflammatory immune response inversely related to increasing temperature. The combination of rationally designed glycolipid adjuvants with the thermoresponsive material polyN-isopropyl acrylamide affords an adjuvant wherein potency itself is manipulated in response to temperature. Additionally, translation of established acid-labile phorsphoramidate linker chemistry to hydrophilic polymeric carriers has successfully imparted their selective release profiles to macromolecular systems, expanding the repertoire of delivery strategies for anti-cancer therapeutics with efforts to improve circulation times and availability of traditionally hydrophobic chemotherapeutics. As stimuli-responsive biomaterials continue to progress, their capacity to reshape immunotherapy and therapeutic administration holds immense prospects, restructuring the landscape of treatment methodologies and auguring heightened prognoses for patients.
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Details
- Title
- Synthesis and Performance of Stimuli-Responsive Polymeric Biomaterials for Immunological and Therapeutic Application
- Creators
- Aaron T Hendricksen
- Contributors
- Clifford E Berkman (Advisor)Rock J Mancini (Committee Member)Anjali Sharma (Committee Member)Ming Xian (Committee Member)
- Awarding Institution
- Washington State University
- Academic Unit
- Department of Chemistry
- Theses and Dissertations
- Doctor of Philosophy (PhD), Washington State University
- Publisher
- Washington State University
- Number of pages
- 178
- Identifiers
- 99901087336401842
- Language
- English
- Resource Type
- Dissertation