Shanghai Key Laboratory of Advanced Polymeric Materials, Key Laboratory for Ultrafine Materials of Ministry of Education, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237, China.
Colloids Surf B Biointerfaces. 2010 Oct 15;80(2):145-54. doi: 10.1016/j.colsurfb.2010.05.038. Epub 2010 Jun 2.
Core-shell micelles with biodegradability, thermo- and pH-response were successfully demonstrated by poly(2-oxepane-1,5-dione-co-epsilon-caprolactone) (P(OPD-co-CL)) grafted with hydrophilic segments of amine-terminated poly(N-isopropylacrylamide) (At-PNIPAM). To compare with the graft copolymer, P(OPD-co-CL) block PNIPAM polymer was also prepared. The micelles with core-shell structure were formed with both graft and block copolymers by self-assembly in aqueous solutions, of which PNIPAM shell is thermo-response. Furthermore, P(OPD-co-CL)-g-PNIPAM also showed pH-sensitivity, which was attributed to the acid-cleavable property of the hydrazone bond. The low critical micelle concentrations (CMCs) of graft polymers and block polymers were 6.7 mg/L and 14.3mg/L, respectively, which indicated the formation of stable micelles. Both drug-free and drug-loaded micelles were in uniformly spherical shape observed by transmission electron microscopy (TEM). The sizes of the drug-free and drug-loaded micelles prepared from graft polymer were 123.5 nm and 146.5 nm, respectively, and the sizes of those prepared from block polymer were 197.5 nm and 211.5 nm, respectively. The lower critical solution temperature (LCST) for the graft polymer was 34.3 degrees C, while that for the block polymer was 28.1 degrees C, demonstrating a thermo-response. The graft polymeric micelles exhibited thermo-triggered decelerated release at pH 7.4, and pH-triggered accelerated release at 25 degrees C in vitro release test, indicating that the graft polymeric micelles could be a promising site-specific drug delivery system for enhancing the bioavailability of the drug in targeted pathological areas.
成功制备了具有生物降解性、温敏性和 pH 响应性的核壳型胶束,其亲水段为端氨基聚(N-异丙基丙烯酰胺)(At-PNIPAM)接枝的聚(2-氧杂环庚烷-1,5-二酮-共-ε-己内酯)(P(OPD-co-CL))。为了与接枝共聚物进行比较,还制备了 P(OPD-co-CL)嵌段 PNIPAM 聚合物。通过自组装在水溶液中形成具有核壳结构的胶束,其中 PNIPAM 壳具有温敏性。此外,P(OPD-co-CL)-g-PNIPAM 还表现出 pH 敏感性,这归因于腙键的酸裂解性质。接枝聚合物和嵌段聚合物的低临界胶束浓度(CMC)分别为 6.7mg/L 和 14.3mg/L,表明形成了稳定的胶束。通过透射电子显微镜(TEM)观察到,无药物和载药胶束均呈均匀的球形。从接枝聚合物制备的无药物和载药胶束的粒径分别为 123.5nm 和 146.5nm,从嵌段聚合物制备的胶束的粒径分别为 197.5nm 和 211.5nm。接枝聚合物的低临界溶液温度(LCST)为 34.3℃,而嵌段聚合物的 LCST 为 28.1℃,表现出温敏性。在体外释放试验中,接枝聚合物胶束在 pH 7.4 下表现出温度触发的缓慢释放,在 25℃下表现出 pH 触发的加速释放,表明接枝聚合物胶束可以作为一种有前途的靶向药物传递系统,以提高药物在靶向病理区域的生物利用度。