Design of Polyelectrolyte-Based Thin Films for the Surface-Mediated Release of Macromolecular Agents

The work described in this thesis is focused on the fabrication and characterization of polymer thin films with potential applications in the areas of controlled drug delivery and biomedical research. Specifically, the work described here investigates polymer films fabricated using layer-by-layer assembly, a technique that involves the alternate deposition of polymer layers onto a surface to form multilayered film architectures. The multilayered films characterized in this thesis are divided into two classes: (i) multilayered polyelectrolyte films ('polyelectrolyte multilayers' or PEMs) which are assembled via electrostatic interactions, and (ii) covalently crosslinked multilayered films that are fabricated by covalent bonds formed between adjacent layers.;The majority of the work described in this thesis is focused on the incorporation of biomacromolecules into multilayered polyelectrolyte films and characterization of the ability of these thin films to release the biomacromolecules when incubated under physiologically relevant conditions. The data presented here demonstrate the ability to incorporate proteins, peptides, and nucleic acids (DNA and siRNA) into multilayered assemblies fabricated using polyelectrolytes tailored toward the incorporation and subsequent controlled release of each specific type of macromolecule. The multilayered films fabricated in these contexts can be used to immobilize biomacromolecules on surfaces and subsequently promote the controlled, localized, and surface-mediated release of these bioactive agents. Films fabricated using this approach were investigated in the contexts of gene delivery, knockdown of gene expression using RNA interference, and the development of antifungal films with the potential to reduce catheter-associated infections. The ability of this approach to promote surface-mediated transdermal delivery of proteins and DNA in porcine cadaver skin using microneedle arrays coated with these multilayered films is also described. A final investigation describes the incorporation of auxiliary agents into ultrathin films to achieve faster release profiles for applications that may require the rapid insertion and removal of biomedical devices. The second class of multilayered films described in this thesis demonstrates the ability to use layer-by-layer assembly to fabricate covalently crosslinked thin films on sacrificial, colloidal templates to create reactive, hollow microcapsules for use in applications including catalysis, drug delivery, and imaging, or in other areas of fundamental research.