| dc.description.abstract | Polymers possess many properties which make them ideal for drug delivery platforms, yet both the development and manufacturing creates challenges toward the material advancement. By governing the functionality of polymers and their crosslinked networks, the goal of this work is to develop practical methods for utilizing polymer materials in drug delivery applications. As such, we focused on the development and application of biocompatible and biodegradable polymer building blocks, including polyester, polyacrylate, and polyglycidol, with high degree of functionality for greater tunability. Several promising strategies toward more advanced drug delivery matrices were developed, including targeted nanoparticle platforms, a novel tunable nanoparticle network, and a combination drug delivery system utilizing both nanoparticles and prodrugs. The design of an orthogonal synthetic pathway afforded access to a versatile targeted nanocarrier, allowing for direct delivery of encapsulated drugs within the nanoparticle. This strategy was successfully applied to the development of nanocarriers for the treatment of diabetes and cardiovascular disease via attachment of targeting peptide ligands in addition to imaging agents. Furthermore, we have addressed the challenges of poor drug loading and complicated synthetic pathways by developing practical synthetic methods for fabricating nanoparticles in precise dimensions and densities which can achieve high drug loading capacity. We also explored an approach to the dual delivery of synergistic therapeutic combinations through the conjugation of a toxic small molecule, formaldehyde, to polymers for sustained-release delivery in combination with doxorubicin-loaded nanoparticles for improved antitumor efficacy. Moreover, both nanoparticle and prodrug platforms were investigated for their tunability of nano- and macroscale properties, such as diameter, density, molecular weight, dispersity, and degradation. Finally, these materials were evaluated for their drug release behavior in different environmental conditions, such as acidic and neutral pH ranges, and were found to exhibit varied release profiles, allowing for highly tailorable performance. The polymer materials developed in this work have great potential within the field of drug delivery due to their improved drug capacity, tunability of release, and stimuli-responsive behavior. | |
