A high capacity polymeric micelle of paclitaxel: Implication of high dose drug therapy to safety and in vivo anti-cancer activity

作者：He Zhijian; Wan Xiaomeng; Schulz Anita; Bludau Herdis; Dobrovolskaia Marina A; Stern Stephan T; Montgomery Stephanie A; Yuan Hong; Li Zibo; Alakhova Dania; Sokolsky Marina; Darr David B; Perou Charles M; Jordan Rainer; Luxenhofer Robert; Kabanov Alexander V

来源：Biomaterials, 2016, 101: 296-309.

DOI：10.1016/j.biomaterials.2016.06.002

• Polyoxazolines
• Paclitaxel nanoformulation
• In vitro
• In vivo
• Efficacy
• Multi-drug resistant cancer

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.

• 出版日期2016-9