Topic：Poly (2-oxazoline) Based Nanoformulations with Superior Safety and Efficacy In Vivo
Speaker： Prof. Rainer Jordan
The poor solubility of many anticancer drugs including paclitaxel (PTX), the commercially most successful anticancer drug, has long been hampering the development of suitable formulations. Here, we report on a nanoformulation of PTX with a poly(2-oxazoline) triblock copolymer (POx), which is characterized by a facile preparation, extraordinary high drug loading of 50 % wt. and PTX solubility of up to 45 g/L that calculates to a solubility increase by a factor of 50.000. The formulation shows excellent shelf stability and defined, sub-100 nm size spherical micelles. We observe favorable in vitro and in vivo safety profiles and a higher maximum tolerated dose as compared to PTX formulations currently used in chemotherapy. Pharmacokinetic analysis reveals that the higher dose administered leads to a higher exposure of the tumor to PTX. As a result, we observed a dramatically improved therapeutic outcome in orthotopic tumor models including the very aggressive “T11” mouse claudin-low breast cancer orthotopic, syngeneic transplants which is considered as a clinical faithful cancer model.
Since 2009 Professor (W3), Chair of Macromolecular Chemistry, TU Dresden
2004 - 2008 Assistant Professor (Akadem. Oberrat), TU München
1999 - 2004 Habilitation, TU München with Prof. Oskar Nuyken, Lehrstuhl für Makromolekulare Stoffe
1998 - 2008 Assistant Professor, Polytechnic University, Brooklyn, NY, USA
1996 - 1998 DFG-PostDoc-Fellow at Polytechnic University, Brooklyn, NY with Prof. Abraham Ulman
1993 - 1996 Dr. rer. nat. in Chemistry at the Univ. Mainz and C.N.R.S., Paris, France
1989 - 1990 IAS Fellow at Kyoto University, Japan
1986 - 1993 Study of Chemistry (Dipl. Chem.) at the Universität Mainz, Germany
Organic chemistry, Polymer chemistry, Surface chemistry and physics, Living and controlled polymerizations, Nanomedicine, Regenerative Therapies, Biomaterials, Polymers for opto-electronics
Honors & Awards
2012 Elkin-Lecture of the Winship Cancer Institute
2000 Dr. Herrmann Schnell Prize of the GDCh
1996 DFG-PostDoc Fellow
1993 DAAD-PROCOPE Fellow
1989 IAS Fellow of the DAAD
List of 5 selected publications
(>160 publications in referred journals, >150 invited lectures, 7 patents, h-Index ≧ 47, citations≧6000)
F. Manzenrieder, R. Luxenhofer, M. Retzlaff, R. Jordan, M. G. Finn, Angew. Chem. Int. Ed. 2011, 50, 2601-2605.
M. Steenackers, A. M. Gigler, N. Zhang, F. Deubel, M. Seifert, L. H. Hess, C. H. Y. X. Lim, K. P. Loh, J. A. Garrido, R. Jordan, M. Stutzmann, I. D. Sharp, J. Am. Chem. Soc. 2011, 133, 10490-10498.
A. Schulz, S. Jaksch, R. Schubel, E. Wegener, Z. Di, Y. Han, A. Meister, J. Kressler, A. V. Kabanov, R. Luxenhofer, C. M. Papadakis, R. Jordan, ACS Nano 2014, 8, 2686-2696.
T. Zhang, Y. Du, J. Kalbacova, R. Schubel, R. D. Rodriguez, T. Chen, D. Zahn, R. Jordan, Polym. Chem. 2015, 6, 8176-8183.
D. Hafner, L. Ziegler, M. Ichwan, T. Zhang, M. Schneider, M. Schiffmann, C. Thomas, K. Hinrichs, R. Jordan, I. Amin, Adv. Mater. 2016, 28, 1489-1494.