A high capacity polymeric micelle of paclitaxel: Implication of high dose drug therapy to safety and in vivo anti-cancer activity.
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| Abstract |
The poor solubility of paclitaxel (PTX), the commercially most successful anticancer drug, has long been hampering the development of suitable formulations. Here, we present translational evaluation of a nanoformulation of PTX, which is characterized by a facile preparation, extraordinary high drug loading of 50% wt. and PTX solubility of up to 45 g/L, excellent shelf stability and controllable, sub-100 nm size. We observe favorable in vitro and in vivo safety profiles and a higher maximum tolerated dose compared to clinically approved formulations. Pharmacokinetic analysis reveals that the higher dose administered leads to a higher exposure of the tumor to PTX. As a result, we observed improved therapeutic outcome in orthotopic tumor models including particularly faithful and aggressive "T11" mouse claudin-low breast cancer orthotopic, syngeneic transplants. The promising preclinical data on the presented PTX nanoformulation showcase the need to investigate new excipients and is a robust basis to translate into clinical trials.
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| Authors | Zhijian He, Xiaomeng Wan, Anita Schulz, Herdis Bludau, Marina A Dobrovolskaia, Stephan T Stern, Stephanie A Montgomery, Hong Yuan, Zibo Li, Daria Alakhova, Marina Sokolsky, David B Darr, Charles M Perou, Rainer Jordan, Robert Luxenhofer, Alexander V Kabanov |
| Journal | Biomaterials (Biomaterials) Vol. 101 Pg. 296-309 (09 2016) ISSN: 1878-5905 [Electronic] Netherlands |
| PMID | 27315213 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't) |
| Copyright | Copyright © 2016 Elsevier Ltd. All rights reserved. |
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