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

被引：157

作者：

He, Zhijian ^{[1
,2
]}

Wan, Xiaomeng ^{[1
,2
]}

Schulz, Anita ^{[3
]}

Bludau, Herdis ^{[3
]}

Dobrovolskaia, Marina A. ^{[4
]}

Stern, Stephan T. ^{[4
]}

Montgomery, Stephanie A. ^{[5
]}

Yuan, Hong ^{[6
]}

Li, Zibo ^{[6
]}

Alakhova, Dania ^{[1
,2
]}

Sokolsky, Marina ^{[1
,2
]}

Darr, David B. ^{[7
]}

Perou, Charles M. ^{[7
]}

Jordan, Rainer ^{[3
]}

Luxenhofer, Robert ^{[8
]}

Kabanov, Alexander V. ^{[1
,2
,9
]}

机构：

[1] Univ N Carolina, Eshelman Sch Pharm, Ctr Nanotechnol Drug Delivery, Genet Med Bldg,Room 1094,Campus Box 7362, Chapel Hill, NC 27599 USA

[2] Univ N Carolina, Eshelman Sch Pharm, Div Mol Pharmaceut, Chapel Hill, NC 27599 USA

[3] Tech Univ Dresden, Dept Chem, Makromol Chem, Mommsenstr 4, D-01069 Dresden, Germany

[4] Leidos Biomed Res Inc, Nanotechnol Characterizat Lab, Frederick Natl Lab Canc Res, Frederick, MD USA

[5] Univ N Carolina, Dept Pathol & Lab Med, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA

[6] Univ N Carolina, Sch Med, Dept Radiol, Chapel Hill, NC 27599 USA

[7] Univ N Carolina, Anim Study Core, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA

[8] Univ Wurzburg, Funct Polymer Mat, Chair Chem Technol Mat Synth, Rontgenring 11, D-97070 Wurzburg, Germany

[9] Moscow MV Lomonosov State Univ, Lab Chem Design Bionanomat, Fac Chem, Moscow, Russia

来源：

BIOMATERIALS | 2016年 / 101卷

关键词：

Polyoxazolines; Paclitaxel nanoformulation; In vitro; In vivo; Efficacy; Multi-drug resistant cancer; BREAST-CANCER; DELIVERY-SYSTEMS; NANOPARTICLE FORMULATION; CREMOPHOR-FREE; PHASE-II; POLY(2-OXAZOLINE); EFFICACY; TUMORS; NK105; TAXOL;

D O I：

10.1016/j.biomaterials.2016.06.002

中图分类号：

R318 [生物医学工程];

学科分类号：

0831 ;

摘要：

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. (C) 2016 Elsevier Ltd. All rights reserved.

引用

页码：296 / 309

页数：14

共 45 条

[11] A Low Protein Binding Cationic Poly(2-oxazoline) as Non-Viral Vector [J].