Multilayered thin films from poly(amido amine)s for controlled delivery

Abstract

Layer-by-layer (LbL) assembly is a versatile and economical method to coat existing biomaterials with multilayered thin films for added functionality. The technique requires at least two complementary macromolecules to be deposited alternately onto a surface, forming thin multiple layers with properties that are customizable through the deposition conditions such as pH, temperature, and ionic strength. As a class of synthetic peptidomimetic polymers that have shown significant promise as therapeutic delivery agent through the ability to interact with DNA, proteins, carbohydrates, and small drug molecules, poly(amido amine)s (PAA) are promising multilayer components. This thesis describes a series of reports on the use of PAA as a component for LbL assembly. The reports describe the study on structure-function relationship of the various PAAs to the build-up profiles, and properties and functionality of the resulting multilayers. The report starts with the pairing of PAAs with DNA to yield multilayer-coated surfaces that can facilitate cell transfection. The optimization of such surface-mediated cell transfection and its successful demonstration on 2D and 3D tissue engineering scaffolds from several common biomaterials are described in the last Chapter. The PAA-multilayers were also studied as drug-eluting surfaces. For this purpose, boronic ester formation was utilized to provide multi-responsive interactions with small drug compounds. In one Chapter, boronic acid-functionalized PAAs were paired with chondroitin sulfate, a natural biopolymer, to entrap alizarin red S, a model for catechol drugs. The multilayer-coated surfaces successfully promote intracellular uptake of polymer-complexed alizarin red S in vitro. In another Chapter, PAA was paired with poly(vinyl alcohol), an FDA-approved biomaterial, to entrap bortezomib, a drug for multiple myeloma. Depending on how the multilayers were fabricated, the therapeutic efficacy could be tuned to differently affect target cells depending on their spatial location. The results in this thesis indicate great promise for poly(amido amine)-based multilayered thin films.