Prof. Rolf Schubert
Liposomes are ideal models for the study of self-aggregation of molecules in biological membranes. Using various liposomal lipid composition, charge, size, and influence of stabilising anchor molecules, we study the interaction of membranes with surfactants and peptides. Surfactant-membrane interaction is a crucial in preparing homogeneous liposomes as well as for reconstitution of membrane proteins. Using cryo-transmission electron microscopy, fluorescence resonance energy transfer and self-quenching fluorescence labels, membranes can be characterised for triggered permeability, phase separation of lipids and proteins and lipid solubilisation.
Active targeting of drugs with nanocarriers:
Liposomes and other nanocarriers are suitable for targeting drugs after intraveneous administration specifically to the site of desired action. The reasons are i) the increased permeation of the particles through the porous endothelia in tumors and inflamed tissues and ii) the specific binding of ligand-modified nanocarriers to specific surface antigens. The cellular association and the intracellular fate of the carriers and the drugs after a particular endocytotic route is then studied, in cooperation with Prof. Regine Süss, by using FACS analysis, confocal fluorescence microscopy or Fourier-transformed spectral imaging
After oral administration drugs are normally absorbed by the small intestine and distributed to various tissues via the blood circulation. To achive high concentration in the large intestine (caecum, colon) and to minimise unwanted side effects, drugs for the therapy of intestinal inflammatory diseases (Morbus Crohn, Colitis ulcerosa) or of colonic cancer should be transported in the intestine without absorption. We are working on polymer-coatings of tablets and pellets, which are stable in the small intestine and are then degraded in the colon by enzymes of the tremendous number of bacteria in the colon. After degradation of the coating the drug is then locally released.
10 selected publications
- Designer amphiphilic proteins as building blocks for the intracellular formation of organelle-like compartments
Huber H, Schreiber A, von Olshausen P, Varga B, Kretz O, Joch B, Barnert S, Schubert R, Eimer S, Kele P, Schíller S
Nat Mater 2014; Nov 2. doi: 10.1038/nmat4118.
- Development and Evaluation of chitosan and chitosan/Kollicoat Smartseal 30 D film-coated tablets for colon targeting
Drechsler M, Garbacz G, Thomann R, Schubert R
Eur J Pharm Biopharm, 2014; doi.org/10.1016/j.ejpb.2014.09.006
- Cellular Studies in Caco-2, MDCKII mdr1 and MDCKII wildtype cells and P-gp ATPase Activity Measurements
Simon S, Schubert R: Inhibitory Effect of Phospholipids on P-Glycoprotein
BBA-mol Cell Biol L 2012;1821: 1111-1123
- Discovery of the inhibitory effect of a phosphatidylinositol derivative on P-glycoprotein by virtual screening followed by in vitro cellular studies
Lucas X, Simon S, Schubert R, Günther S (2013)
PLoS One. 8(4):e60679.
- Lipid transfer mediated by a recombinant pro-sterol carrier protein 2 for the accurate preparation of asymmetrical membrane vesicles requires a narrow vesicle size distribution: A free-flow electrophoresis study.
Holzer M, Momm J, Schubert R (2010).
Langmuir 26 (6), 4142-4151
- Preparative size exclusion chromatography combined with detergent removal as a versatile tool to prepare unilamellar and spherical liposomes of highly uniform size distribution.
Holzer M, Barnert S, Momm J, Schubert R (2009).
J Chromatogr A 1216, 5838-5848
- In vivo monitoring of inflammation after cardiac and cerebral ischemia by fluorine magnetic resonance imaging.
Flögel U, Ding Z, Hardung H, Jander S, Reichmann G, Jacoby C, Schubert R, Schrader J (2008).
Circulation 118, 140-148
- Tresylated PEG-sterols for coupling of proteins to preformed plain or PEGylated liposomes.
Steenpaß T, Lung A, Schubert (2006).
BBA-Biomembranes 1758, 20-28
- Synthesis of a polymer skeleton at the inner leaflet of liposomal membranes: Polymerization of membrane-adsorbed pH-sensitive monomers.
Gutmayer D, Thomann R, Bakowsky U, Schubert R (2006).
Biomacromolecules 7, 1422-1428
- Reconstitution of bactericidal activity in cronic granulomatous disease cells by glucose-oxidase-containing liposomes.
Gerber CE, Bruchelt G, Falk UB, Kimpfler A, Hauschild S, Kuçi S, Bächi T, Niethammer D, Schubert R (2001).
Blood 98, 3097-3105