Biological interactions
Wechselwirkung der entwickelten Polymernanostrukturen mit Zellen und Gewebe
Nanopartikel zur zielgerichteten effizienten Translokation durch gastrointestinale Barrieren (CRC 1278 Polytarget / Project A05)
IBD treatment (Illustration: Fabian Sobotta)
Based on a systematic platform the project aims for the preparation of polymeric nanoparticles, which effectively translocate across gastrointestinal barriers and target macrophages as main pro-inflammatory cells within the mucosa. Our part is the design and synthesis of these polymer nanoparticles, which differ in size and, in particular, in their controlled anisotropic shape. Furthermore these materials will be modified with targeting ligands to enhance translocation efficacy and to maximize the adherence as well as uptake into the desired cells. The nanosized diameter should guarantee an efficient translocation through mucus and epithelium, while the increased lengths and surface area favors the adhesion to the macrophages in mucosal layer.
pH-Responsive polyacrylamides for endosomal escape and cytosolic delivery of biologicals
Endosomal escape (Illustration: Franziska Hausig)
Polymers are exposed to various environments in biological media, such as fluctuating pH values, different redox potentials or variable temperatures. However, these external stimuli can also be exploited to overcome specific barriers during the transport of pharmaceuticals to the desired site of action. Among others, we develop responsive polymers that are protonated/deprotonated and become charged depending on the pH value. Such polymers can, for example, cause a release from the endo- or lysosome as they become increasingly charged in the acidic environment. In order to identify correlations between the basicity of a material and its ability to overcome the endosomal barrier, we have established various release tests using tracer molecules which differ in molar mass and functionality (e.g. calcein, dextran, proteins, nucleic acids).
In Vitro studies
Polymeric nanoparticles represent a promising material to release active pharmaceutical ingredients continuously or selectively at the site of action. In addition to biocompatibility, we characterize various biological interactions, for example the uptake into cells or the efficiency of drug delivery. Among others, standardized tests (ISO-10993-5) are used to evaluate the cytotoxicity of novel polymers. Hemocompatibility is also tested according to the current state of the art. We further investigate the ability of these novel materials to deliver various compounds, including small molecules, macromolecules, proteins and nucleic acids to the desired site of action within the cell. Therefore, new methods and assays are developed to establish a more detailed structure-property relationship. For these purposes we have a large number of cell lines from various mammals at our disposal.