高载药诱导的聚2-噁唑啉胶束形态变化研究  

Study of morphological changes of poly(2-oxazoline)micelles induced by high loading of drugs

作　　者：徐敏[1] 邹豪[1] 高静[1,2] 

机构地区：[1]第二军医大学药学院药剂学教研室,上海200433 [2]军事医学科学院毒物药物研究所,北京100850

出　　处：《第二军医大学学报》2017年第2期155-160,共6页Academic Journal of Second Military Medical University

基　　金：国家"重大新药创制"专项(2013ZX09J13109-04B)~~

摘　　要：目的制备载紫杉醇的聚2-噁唑啉纳米胶束,通过改变投药量考察药物引起的胶束形态变化,以期构建新型的高荷载嵌段共聚物胶束递药系统。方法采用薄膜水化法制备聚2-噁唑啉载药胶束,以粒径、包封率和载药量等评价其理化性质,采用膜透析法考察其体外释药特性,利用CCK-8法测定其细胞毒性。结果随着投药比由80∶100(紫杉醇与聚2-噁唑啉质量比)增加至110∶100,胶束逐渐由球形延长,变为蠕虫状。投药比为80∶100时,球形胶束的平均粒径为(43.17±0.95)nm,包封率为(88.81±2.93)%,载药量为(40.49±2.03)%;投药比增加至110∶100后,所得蠕虫状胶束的平均粒径为(107.83±1.51)nm,包封率为(77.08±0.97)%,载药量为(40.34±0.51)%。球形和蠕虫状胶束在磷酸盐缓冲液中24h的累积释放量分别达到(76.58±3.07)%和(77.66±1.00)%,在含2%小牛血清白蛋白的PBS溶液中24h的累积释放量高达(100.31±1.80)%和(99.73±2.56)%。球形胶束和蠕虫状胶束对人肺腺癌细胞A549的杀伤IC50值分别为0.336和0.342μg/mL。结论成功制备了高荷载的球形和蠕虫状载药胶束,体外细胞毒性实验证明其具备抗肿瘤活性。Objective To prepare the paclitaxebloaded poly（2-oxazolyl） nano-micelles and to investigate the morphological changes of nano-mieelles after changing drug dosage, so as to establish a novel block eopolymer mieelles delivery system with high loading capacity. Methods The paelitaxel-loaded poly（2-oxazolyl） nano-mieelles were prepared using filming-rehydration method. The physical and chemical properties of the prepared nano-micelles, including particle size, encapsulation efficiency and drug loading efficiency, were characterized. The in vitro release characteristics of the prepared nano-micelles were investigated by membrane dialysis method, and the cytotoxicity was determined by CCK-8 method. Results The morphology of micelles gradually extended from spherical to worm-like when the mass ratio of paclitaxel and poly（2-oxazoline） increased from 80 z 100 to 110 ： 100. The particle size, encapsulation efficiency and drug loading efficiency of spherical micelles were （43. 17± 0. 95） nm, （88. 81±2. 93）% and （40. 49±2. 03）%, respectively, while those of worm-like micelles were （107. 83±1. 51） nm, （77, 08±0. 97）% and （40. 34±0. 51）%, respectively. The 24 h cumulative release rates of spherical mieelles and worm-like micelles in PBS were （76. 58±3. 07）% and （ 77. 66±1.00）%, respectively ; meanwhile, those in PBS with 2 % bovine serum albumin were up to （100. 31±1. 80）% and （99. 73±2. 56）%, respectively. The IC50 values of sphere micelles and worm-like micelles on human lung adenocarcinoma cell line A549 were 0. 336 μg/mL and 0. 342 μg/mL, respectively. Conclusion Paclitaxel-loaded spherical miceUes and worm-like micelles with high loading capacity have been successfully prepared. In vitro cytotoxicity results have found that both micelles have anti-tumor activities.

关 键 词：紫杉醇 聚2-噁唑啉 球形胶束 蠕虫状胶束 

分 类 号：R943.4[医药卫生—药剂学]