Triple-stimuli (pH/thermo/reduction) sensitive copolymers for intracellular drug delivery
Triple-stimuli (pH/thermo/reduction) sensitive copolymers for intracellular drug delivery
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用于细胞内药物输送的三重刺激（pH/热/还原）敏感共聚物
DOI：
10.1039/c3tb00424d
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发表时间：
2013-01-01
影响因子：
7
通讯作者：
Zhuo, Renxi
中科院分区：
文献类型：
--
作者：
Huang, Xiangang;Jiang, Xulin;Zhuo, Renxi
报道了基于嵌段共聚物p（PEG-MEMA-co-Boc-Cyst-MMAm-co-VI）-b-PEG（PPBV）的新型温度、pH和还原敏感性聚合物胶束的开发，用于抗癌药物的细胞内递送。通过DLS和UV-Vis实验观察到PPBV的pH/温度响应行为。通过快速加热方法制备的PPBV胶束在PBS（pH 7.4，37 ℃）中稳定超过48小时，并且在血清存在下稳定至少12小时。通过简单的加热方法将紫杉醇（PTX）以高包封率（>85%）负载到PPBV胶束中，导致高载药量（高达26wt%）。载PTX的胶束显示在PBS中缓慢的药物释放和暴露于弱酸性pH或还原性环境后快速释放。随着PTX浓度的增加，载PTX的胶束对HepG 2细胞显示出更高的细胞毒性，而空胶束被发现是无毒的。这些多敏感性聚合物胶束可能作为细胞抑制药物的有前途的载体。
The development of novel thermo-, pH- and reduction-sensitive polymeric micelles based on a block copolymer p(PEG-MEMA-co-Boc-Cyst-MMAm-co-VI)-b-PEG (PPBV) for the intracellular delivery of anticancer drugs is reported. The pH/temperature-responsive behaviour of PPBV is observed by both DLS and UV-Vis experiments. The PPBV micelles prepared by a quick heating process are stable in PBS (pH 7.4, 37 degrees C) for over 48 h and are stable in the presence of serum for at least 12 h. Paclitaxel (PTX) was loaded into the PPBV micelles with a high encapsulation efficiency (>85%), resulting in a high drug loading content (up to 26 wt%) by a simple heating method. The PTX-loaded micelles show slow drug release in PBS and rapid release after exposure to a weakly acidic pH or reductive environment. The PTX-loaded micelles showed higher cytotoxicity against HepG2 cells with increasing PTX concentration, whereas empty micelles are found to be non-toxic. These multi-sensitive polymeric micelles may serve as promising carriers for cytostatic drugs.