Analyzing the interactions of thermoresponsive coacervate-forming biodegradable polyester encapsulation on model protein structure and activity

<p>Protein therapeutics hold high efficacy in treatment for various diseases including cancer and diabetes. However, the treatment cost is generally higher than other therapeutics mainly due to <em>in vivo</em> protein degradation. This drawback creates demand for more efficient delivery methods to preserve the function and integrity of protein therapeutics. Thermoresponsive coacervate-forming biodegradable polyesters (TR-PEs) are a thermoresponsive molecular packaging system used in protein therapeutic research. The term coacervate refers to a phase-separated solution in which a dense polymer phase separates from the aqueous phase to form nanodroplets within solution, capturing bioactive molecules. Limited research demonstrates if TR-PEs can encapsulate and preserve a larger protein’s activity and how these TR-PEs interact with a protein on the biophysical level. It was determined that TR-PEs encapsulated and released active β-galactosidase enzyme. Encapsulation was visualized using confocal fluorescence microscopy and by labeling β-galactosidase with fluorescein isothiocyanate. Interactions between ¹⁵N-isotopically labelled human ubiquitin c and TR-PEs were investigated through variable temperature nuclear magnetic resonance. It was interpreted that TR-PEs non-specifically interact with ¹⁵N-ubiquitin and that various pendant groups within a given polymer resulted in non-significant differences. Although TR-PEs may not be specifically interacting with the model cargos, demonstrating that TR-PEs capture and release an unaltered, complex protein exemplifies the viability of using TR-PEs for future therapeutic packaging and possible delivery.</p>

Name thesis:degree_name

Master of Science in Chemical Sciences (MSCB)

Level thesis:degree_level

Thesis

Discipline thesis:degree_discipline

Chemistry

Year dc:date.available

2022

Author dc:creator

• Casterline, Conner

Contributors dc:contributor

• Thomas C. Leeper
• Carol A. Chrestensen
• Christopher R. Dockery

• Therapeutic encapsulation
• enzymatic activity
• confocal microscopy
• Chemistry

Repository record dc:identifier

https://digitalcommons.kennesaw.edu/mscs_etd/51

OAI identifier oai:identifier

oai:digitalcommons.kennesaw.edu:mscs_etd-1052