Wang Zheng, Chen Chao, Zhang Qi, Gao Min, Zhang Ju, Kong Deling, Zhao Yanjun
Tianjin Key Laboratory for Modern Drug Delivery & High Efficiency, School of Pharmaceutical Science & Technology, Tianjin University, Tianjin, China.
Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.
Eur J Pharm Biopharm. 2015 Feb;90:53-62. doi: 10.1016/j.ejpb.2014.11.002. Epub 2014 Nov 13.
To precisely manipulate the intracellular delivery of pleiotropic curcumin, this work reports two types of acid-responsive polymer-curcumin conjugates with different structures. One or two amphiphilic poly(ethylene glycol)-co-poly(lactic acid) (PEG-PLA) copolymer(s) were linked to curcumin via pH-liable hydrazone, producing a linear or phospholipid-like conjugate, respectively. Both conjugates efficiently self-assembled into micellar nanocarriers with enhanced stability in contrast to the paralleling PEG-PLA micelles. In comparison to the micelles assembled by phospholipid-like conjugates, the linear conjugate micelles exhibited similar size, doubled loading dose, higher release rate, and hence enhanced cellular uptake and cytotoxicity at the cost of increased critical micelle concentration. This work highlighted the importance of precise tuning of polymer-drug conjugate architecture in determining the pharmaceutical properties and thus delivery efficiency of the corresponding conjugate micelles.
为了精确控制多效姜黄素的细胞内递送，本研究报道了两种具有不同结构的酸响应型聚合物-姜黄素共轭物。一或两个两亲性聚（乙二醇）-共-聚（乳酸）（PEG-PLA）共聚物通过对pH敏感的腙键连接到姜黄素上，分别产生线性或磷脂样共轭物。与平行的PEG-PLA胶束相比，两种共轭物均能有效地自组装成具有增强稳定性的胶束纳米载体。与由磷脂样共轭物组装的胶束相比，线性共轭物胶束表现出相似的尺寸、双倍的负载剂量、更高的释放速率，因此以增加的临界胶束浓度为代价增强了细胞摄取和细胞毒性。这项工作突出了精确调节聚合物-药物共轭物结构在确定相应共轭物胶束的药物性质从而递送效率方面的重要性。
