Hydrogen bonding-enhanced micelle assemblies for drug delivery
Hydrogen bonding-enhanced micelle assemblies for drug delivery
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DOI：
10.1016/j.biomaterials.2010.07.018
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发表时间：
2010-11-01
期刊：
影响因子：
14
通讯作者：
Hedrick, James L.
中科院分区：
文献类型：
--
作者：
Kim, Sung Ho;Tan, Jeremy P. K.;Hedrick, James L.
由2，2-二(羟甲基)丙酸衍生的功能化环状碳酸酯的开环聚合(ROP)允许在嵌段共聚物中引入氢键尿素官能团，具有潜在的超分子药物输送系统的应用前景。聚乙二醇聚(乙基无规尿素碳酸酯)(PEGP(e1-x-U-x)C)嵌段共聚物具有很强的氢键功能，不仅使嵌段共聚物在水环境中的临界胶束浓度(CMC)降低到1/4x，而且在不稳定的情况下，还提高了胶束和负载Dox的胶束的动力学稳定性。观察到抗癌药物阿霉素的加入影响了嵌段共聚物在水中的胶束化过程，并导致200 nm以上载药胶束的尺寸突然增大。在含尿素嵌段共聚物/Dox胶束中，这一现象在药物输送应用中可能是一个重大缺陷，得到了显著缓解，同时显著改善了载药量。体外释药曲线显示，随着尿素含量的增加，药物释放速率略有下降。在400 mg/L浓度下，嵌段共聚物对HEK293和HepG2细胞没有明显的细胞毒作用，而Dox胶束对HepG2细胞有明显的杀伤作用。(C)2010爱思唯尔有限公司。保留所有权利。
Ring-opening polymerization (ROP) of functionalized cyclic carbonates derived from 2,2-bis(methylol) propionic acid (bis-MPA) allows for incorporation of H-bonding urea-functional groups into block copolymers with a potential application of supramolecular drug-delivery systems. The strong H-bonding functionalities of poly(ethylene glycol)-block-poly(ethyl-random-urea carbonate) (PEG-P(E1-x-U-x)C) block copolymers not only lowered critical micelles concentration (cmc) of the block copolymer (to 1/4x) in aqueous environment compared to conventional PEG-poly(trimethylene carbonate) (PEG-PTMC) block copolymer without the non-covalent stabilization, but also improved kinetic stability of micelles and Dox-loaded micelles in the presence of a destabilizing agent. It was observed that the incorporation of anticancer drug doxorubicin affected the micellization process of block copolymers in water and caused a sudden increase in sizes of drug-loaded micelles above 200 nm. This phenomenon that can be a significant drawback in drug delivery applications was considerably mitigated in urea-bearing block copolymer/Dox micelles with simultaneously accompanying a significant improvement in drug loading. In vitro drug release profile showed that the increase in urea content led to a slight decrease in Dox release rate. Block copolymer did not have any significant cytotoxicity against HEK293 and HepG2 cells up to 400 mg/L Importantly, Dox-loaded micelles exerted cytotoxic effect against HepG2 cells. (c) 2010 Elsevier Ltd. All rights reserved.