A high capacity polymeric micelle of paclitaxel: Implication of high dose drug therapy to safety and in vivo anti-cancer activity
| Autor: | Robert Luxenhofer, Zibo Li, Herdis Bludau, David B. Darr, Stephanie A. Montgomery, Charles M. Perou, Hong Yuan, Alexander V. Kabanov, Rainer Jordan, Xiaomeng Wan, Anita Schulz, Marina Sokolsky, Zhijian He, Daria Y. Alakhova, Stephan T. Stern, Marina A. Dobrovolskaia |
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| Rok vydání: | 2016 |
| Předmět: |
Drug
Paclitaxel media_common.quotation_subject Biophysics Breast Neoplasms Bioengineering 02 engineering and technology Pharmacology 010402 general chemistry 01 natural sciences Micelle Article Biomaterials Mice chemistry.chemical_compound Breast cancer Pharmacotherapy In vivo Animals Humans Medicine Oxazoles Micelles media_common Ovarian Neoplasms Drug Carriers Mice Inbred BALB C business.industry Cancer 021001 nanoscience & nanotechnology medicine.disease Antineoplastic Agents Phytogenic 0104 chemical sciences chemistry Mechanics of Materials Ceramics and Composites Female 0210 nano-technology business Drug carrier |
| Zdroj: | Biomaterials. 101:296-309 |
| ISSN: | 0142-9612 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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