Author ORCID Identifier

Year of Publication


Degree Name

Doctor of Philosophy (PhD)

Document Type

Doctoral Dissertation




Chemical and Materials Engineering

First Advisor

Dr. Thomas D. Dziubla


Polymers have proven to be a viable platform to facilitate the controlled and targeted release for a variety of therapeutic agents. Polymeric prodrugs are a growing area of drug delivery in which active pharmaceutical ingredients are covalently linked to a polymeric form in an effort to enhance stability, delivery, and pharmacology. One naturally occurring class of active ingredients, known as polyphenols, can potentially offer a vast array of beneficial therapeutic properties. However, the therapeutic efficacy of these compounds is severely limited due to poor solubility and bioavailability as well as an oxidative and thermal instability. To improve the efficacy of these beneficial active ingredients, a delivery system needs to be used to ensure polyphenols reach the site of action while retaining their native activity. Incorporation of polyphenols into polymers has demonstrated promise in remedying these shortcomings. Poly(beta amino esters), or PβAEs, allow for incorporation of the polyphenol into the polymer backbone. This helps not only protect the compound from premature degradation, but also increases its solubility. Since the polymer degrades through hydrolysis at the ester bonds, it can facilitate a controlled, tunable delivery of the unmodified polyphenol.

Much of the previous work with polyphenolic PβAEs has surrounded the development of crosslinked films. While these polymers demonstrated retention of the polyphenol’s native activity, the networked structure limited the overall processability of the polymer. These PβAE systems have been cryomilled into microparticles or directly synthesized into nanogels to facilitate certain routes of delivery. However, the incorporation of these polymers into a larger range of applications such as the development of homogenous creams, coatings, or castings can be difficult. To increase the processing options of these polymers, PβAEs were synthesized to be soluble in organic solvents. Whereas crosslinked polymers tend to swell in organic solvents, the synthesized branched PβAEs solubilized to create a dope solution. This polymeric solution was utilized to synthesize nanoparticles, create coatings, and inkjet print thin films. The polyphenolic release and activity from these structures was analyzed to determine effect of processing on release. Additionally, inkjet printed thin films were thermally crosslinked to assess stability of the branched and crosslinked polymers. By increasing the polymer solubility, novel PβAE delivery methods were developed and potentially facilitate further tuning of degradation and polyphenol release to suit specific applications.

Digital Object Identifier (DOI)

Funding Information

This work was supported by National Institutes of Health Small Business Innovation Research Grant (R44DE023523) and a Kentucky State Matching Grant from 2017-2022.

Available for download on Wednesday, August 16, 2023