Gong ChangYang, Shi Shuai, Dong PengWei, Kan Bing, Gou MaLing, Wang XianHuo, Li XingYi, Luo Feng, Zhao Xia, Wei YuQuan, Qian ZhiYong
State Key Laboratory of Biotherapy, West China Hospital, and School of Life Sciences, Sichuan University, Chengdu 610041, China.
Int J Pharm. 2009 Jan 5;365(1-2):89-99. doi: 10.1016/j.ijpharm.2008.08.027. Epub 2008 Aug 28.
In this work, a series of biodegradable triblock poly(ethylene glycol)-poly(epsilon-caprolactone)-poly(ethylene glycol) (PEG-PCL-PEG, PECE) copolymers were successfully synthesized by ring-opening copolymerization, and were characterized by (1)H NMR, FT-IR, GPC, and DSC. Aqueous solutions of PECE copolymers underwent thermosensitive sol-gel-sol transition as temperature increases when the concentration was above corresponding critical gel concentration (CGC). Sol-gel-sol phase transition diagrams were recorded using test tube inverting method, which depended on hydrophilic/hydrophobic balance in macromolecular structure, as well as some other factors, including topology of triblock copolymers and solution composition of the hydrogel. As a result, the sol-gel-sol transition temperature range could be varied, which might be very useful for its application as injectable drug delivery systems. The in vivo gel formation and degradation behavior was conducted by injecting aqueous PECE solution into KunMing mice subcutaneously. In vitro degradation behavior, in vitro drug release behavior, and cytotoxicity were also investigated in this paper. Therefore, owing to great thermosensitivity and biodegradability of these copolymers, PECE hydrogel is believed to be promising for in situ gel-forming controlled drug delivery system.
在本研究中,通过开环共聚成功合成了一系列可生物降解的三嵌段聚(乙二醇)-聚(ε-己内酯)-聚(乙二醇)(PEG-PCL-PEG,PECE)共聚物,并通过¹H NMR、FT-IR、GPC和DSC对其进行了表征。当浓度高于相应的临界凝胶浓度(CGC)时,PECE共聚物的水溶液随着温度升高会发生热敏性溶胶-凝胶-溶胶转变。采用试管倒置法记录溶胶-凝胶-溶胶相转变图,该转变图取决于大分子结构中的亲水/疏水平衡以及其他一些因素,包括三嵌段共聚物的拓扑结构和水凝胶的溶液组成。结果,溶胶-凝胶-溶胶转变温度范围可以变化,这对于其作为可注射药物递送系统的应用可能非常有用。通过将PECE水溶液皮下注射到昆明小鼠体内来研究其体内凝胶形成和降解行为。本文还研究了其体外降解行为、体外药物释放行为和细胞毒性。因此,由于这些共聚物具有很高的热敏性和生物降解性,PECE水凝胶被认为在原位凝胶形成控释药物递送系统方面具有广阔前景。