Du Jin-Zhi, Tang Ling-Yan, Song Wen-Jing, Shi Yue, Wang Jun
Department of Polymer Science and Engineering, Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, and Department of Chemistry, University of Science and Technology of China, Hefei, Anhui 230027, People's Republic of China.
Biomacromolecules. 2009 Aug 10;10(8):2169-74. doi: 10.1021/bm900345m.
Brush polymers PHEMA-g-(PCL-b-PEG) with poly(2-hydroxyethyl methacrylate) (PHEMA) as the backbone and poly(epsilon-caprolactone)-b-poly(ethylene glycol) (PCL-b-PEG) block copolymers as side chains were synthesized and evaluated as drug delivery vehicles. Two brush polymers were synthesized, and their structures were confirmed by gel permeation chromatography analyses and (1)H NMR measurements. The brush polymers self-assembled into micelles in aqueous solution, and the critical micellization concentrations of brush polymers were 2-fold lower than that of the linear diblock copolymer PCL-b-PEG with structure similar to that of the grafted side chains of brush polymers, indicating the higher aqueous stability of brush polymer micelles. The micelles were spherical with average diameters below 100 nm. Brush polymer micelles exhibited higher loading doxorubicin capacity compared with micelles from linear PCL-b-PEG block copolymer by the dialysis method, and the burst doxorubicin release from the brush polymer micelles was significantly suppressed. Doxorubicin-loaded brush polymer micelles can be effectively internalized by A549 human lung carcinoma cells and slowly released the encapsulated drug molecules as demonstrated by the drug accumulation in cytoplasm, which was opposite to free doxorubicin, which accumulated rapidly in the cell nuclei.
以聚甲基丙烯酸2-羟乙酯（PHEMA）为主链、聚己内酯-b-聚乙二醇（PCL-b-PEG）嵌段共聚物为侧链的刷状聚合物PHEMA-g-(PCL-b-PEG)被合成并作为药物递送载体进行评估。合成了两种刷状聚合物，并通过凝胶渗透色谱分析和¹H NMR测量对其结构进行了确认。刷状聚合物在水溶液中自组装成胶束，刷状聚合物的临界胶束浓度比结构与刷状聚合物接枝侧链相似的线性二嵌段共聚物PCL-b-PEG低2倍，表明刷状聚合物胶束具有更高的水稳定性。胶束呈球形，平均直径低于100 nm。通过透析法，刷状聚合物胶束与线性PCL-b-PEG嵌段共聚物胶束相比表现出更高的阿霉素负载能力，并且刷状聚合物胶束中阿霉素的突释得到了显著抑制。载有阿霉素的刷状聚合物胶束能够被A549人肺癌细胞有效内化，并如细胞质中的药物积累所示缓慢释放包封的药物分子，这与在细胞核中快速积累的游离阿霉素相反。
