Clinical application of polymeric micelles for the treatment of cancer

被引:132
|
作者
Varela-Moreira, Aida [1 ,2 ]
Shi, Yang [3 ]
Fens, Marcel H. A. M. [1 ]
Lammers, Twan [2 ,3 ,4 ]
Hennink, Wim E. [2 ]
Schiffelers, Raymond M. [1 ]
机构
[1] Univ Med Ctr Utrecht, Dept Clin Chem & Haematol, NL-3584 CX Utrecht, Netherlands
[2] Univ Utrecht, Utrecht Inst Pharmaceut Sci, Dept Pharmaceut, NL-3584 CG Utrecht, Netherlands
[3] RWTH Aachen Univ Clin, Inst Expt Mol Imaging, Dept Nanomed & Theranost, D-52074 Aachen, Germany
[4] Univ Twente, MIRA Inst Biomed Technol & Tech Med, Dept Targeted Therapeut, NL-7522 NB Enschede, Netherlands
关键词
CELL LUNG-CANCER; PHASE-II TRIAL; EPIRUBICIN-INCORPORATING MICELLES; BLOCK-COPOLYMER MICELLES; METAL COMPLEX MICELLE; IN-VIVO; ANTITUMOR-ACTIVITY; DRUG-DELIVERY; SOLID TUMORS; GASTRIC-CANCER;
D O I
10.1039/c6qm00289g
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
The in vivo administration of chemotherapeutic drugs is a challenge due to their poor pharmacokinetic (PK) and biodistribution profiles. For this reason, the development of delivery systems capable of targeting these compounds to pathological sites is of great importance. Polymeric micelles (PMs) are good systems for the encapsulation of hydrophobic compounds because their hydrophobic core can accommodate these types of drugs whereas their hydrophilic corona, usually poly(ethylene glycol), enables PMs to circulate for an extended period of time in the bloodstream which allows them to reach tumour tissues by means of the enhanced permeability and retention (EPR) effect. The first generation of PMs was rather unstable and essentially used to solubilize hydrophobic drugs for intravenous (i.v.) administration. More recently, the next-generation of PMs has been developed to achieve high encapsulation and retention of drugs while maintaining prolonged circulation after i.v. administration. These systems are suitable for both passive and active drug targeting. Different approaches have been employed to achieve the abovementioned goals: both non-covalent (hydrophobic and p-p interactions) and chemical (covalent binding of the drug to the polymer backbone and/or crosslinking of the core/shell) strategies have been used to improve the stability in the circulation and to retain the loaded drug in the PM. This will result in the accumulation of the drug at the target site to a greater extent than in healthy tissues and will, in principle, lead to improved therapeutic outcome. Several PM-based formulations are currently being evaluated in clinical trials. In this review, the pre-clinical and clinical outcomes of these PMs are summarized along with the strategies to translate PMs to patients.
引用
收藏
页码:1485 / 1501
页数:17
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