Tailored polymeric nanoparticles for gene delivery and diagnostic
The presented thesis addresses the systematic formulation of polymeric nanoparticles for gene delivery and diagnostic applications, their physicochemical characterization via orthogonal analysis techniques, e.g., dynamic light scattering (DLS), scanning electron microscopy (SEM) and analytical ultracentrifugation (AUC), and the study of their resultant interaction with cells. The formulation of the nanoparticles was realized by nanoprecipitation of the polymers in a manual manner, but also in a high-throughput (HT) approach by the application of pipetting robots. The HT method enabled an efficient screening of various polymer systems with regard to their precipitation behavior and crucial parameters, such as concentration of the initial polymer solution and the solvent/non-solvent ratio in a 96-well plate format. Furthermore, to gain deeper insights into the structure-property relationships of polycations and their resulting nanoparticle formation, dextran was functionalized with different linear poly(ethylene imine)s (lPEI) using various coupling strategies. The resulting cationic polymers were studied in terms of their nanoscale complexation with nucleic acids and their biophysicochemical properties. In addition, a facile combinatorial HT workflow that enables a straightforward but comprehensive characterization of cationic polymers as gene vectors was developed.