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REPORT:Poly(2-oxazoline) Based Nanoformulations with Superior Safety and Efficacy In Vivo

发布者: [发表时间]:2016-09-06 [来源]: [浏览次数]:

Topic:Poly (2-oxazoline) Based Nanoformulations with Superior Safety and Efficacy In Vivo

Speaker: Prof. Rainer Jordan

Abstract:

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.

Bio Information:

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

Research Interests

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. (from: supramol.jlu.edu.cn)

Event Date:Sep 7,2016(Wednesday)

Event Time:09:30am

Venue:Conference Hall 1st Floor, Inorganic Supramolecular Building