期刊
MATERIALS CHEMISTRY FRONTIERS
卷 1, 期 8, 页码 1485-1501出版社
ROYAL SOC CHEMISTRY
DOI: 10.1039/c6qm00289g
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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.
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