Designing Polymers for Biological Interfaces - From Antifouling to Drug Delivery

Abstract: Unspecific interactions, at the interface between a synthetic material and an aqueous biological environment, leading to irreversible protein adsorption can cause to undesired consequences. These include fouling of a boat hull or a triggered immune response. Thus, stealthy materials are a topic that has generated a great deal of interest in the scientific community. This work deals with the design of networks, nanoparticles, and surfaces containing poly(ethylene glycol) (PEG), known for its resistance to protein adsorption and non-toxic nature. Initially, PEG-based networks, hydrogels, were synthesized using photoinduced thiol-ene chemistry in order to afford coatings targeted for marine antifouling applications. By varying the length of the PEG chain, curing chemistry, cross-linker as well as hydrolytical stability, a library of hydrogel coatings was produced. The coatings were subsequently characterized with respect to curing efficiency, thermal and mechanical properties, and aqueous stability. Furthermore, the antifouling properties of coatings were evaluated using in vitro tests with proteins, marine bacteria, and diatoms. As a final test the coatings were evaluated in a four month field test. It was found that coatings comprising longer PEG chains displayed enhanced antifouling performance, compared to shorter PEGs. In addition, the choice of cross-linker, curing chemistry, and hydrolytical stability also affected the properties to a great extent. This thesis further deals with the design of amphiphilic linear dendritic hybrids, with PEG as the hydrophilic block. Using non-toxic 2,2-bis(methylol) propionic acid (bis-MPA) based dendrons, bearing click functional cores (alkyne or allyl) and peripheral hydroxyl groups, as macrointitiators for ring-opening polymerization of ?-caprolactone, a library of star branched materials was afforded. As a final step, click functional (azide or thiol) PEGs were attached using copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) or thiol-ene click chemistry. The size of the dendrons was varied from generation 0-4, along with variation of both poly(?-caprolactone) (PCL) length and PEG length. The materials were designed in order to allow a study of the impact of the dendron generation. Finally, the hybrid materials were used for the preparation of micelles, as well as for the formation of honeycomb membranes. The micelles critical micelle concentration, size and drug loading capacity were shown to be highly dependent on the generation of the dendron. The generation of the dendron also had a profound effect on the ability of the hybrid materials to form ordered honeycomb membranes, and hybrid materials of the 3rd generation yielded the most highly ordered membranes.