Boronic acid functionalized polymers are a very interesting class of materials capable of forming reversible covalent boronic esters. With boronic acids reversible binding of diols and polyols, including carbohydrates, is possible. Although such polymers are promising biomaterials, they are only rarely explored. Thus the goal of this research was to investigate the potential of boronic acid functionalized polymers for biomedical applications. In the first part of this thesis, phenylboronic acids were introduced into the side chains of disulfide containing poly(amido amine)s (SS-PAAs), a promising class of polymers for plasmid DNA and siRNA delivery. Polyplex formation and stability, and transfection efficiency and cell viability of these novel boronated polyplexes were evaluated in vitro. Their capacity for complexation with nucleic acids into polyplexes, polyplex stability, transfection efficiency, and cell viability of cells treated with these polymers were evaluated. These novel boronated polymers offer new possibilities for combined drug and gene delivery. Alizarin red was selected as model drug compound as it is capable of forming a reversible covalent fluorescent ester with boronic acids. Similarly, FITC-labeled dextran was used to form boronic esters. Both strategies allowed for the visualization of the polymeric nanoparticles and polyplexes and made it possible to study the particle uptake by confocal microscopy and FACS. In the second part of this thesis, boronic acid functionalized polymers were found to form strong gels with poly(vinyl alcohol). The thermo-reversible, pH-responsive, and glucose-responsive properties of these gels could be tuned by varying the architecture of the boronic acid and by selecting different polymeric backbones, including poly(amido amine)s, Jeffamines, and multi-arm PEGs. Altogether, it can be concluded that incorporating boronic acid moieties in polymers results in new materials (nanoparticles and hydrogels) with unique properties that may ultimately result in new therapies.
|Award date||30 Sep 2011|
|Place of Publication||Enschede|
|Publication status||Published - 30 Sep 2011|