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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 paclitaxel-loaded poly (2-oxazoline) nanomicelles and investigate the drug-induced morphological changes of micelles by changing the dosage, in order to construct a novel high loading block copolymer micellar drug delivery system. Methods Poly (2-oxazoline) drug-loaded micelles were prepared by membrane hydration method. The physical and chemical properties of the drug-loaded micelles were evaluated by particle size, entrapment efficiency and drug loading. The in vitro drug release characteristics were investigated by membrane dialysis. Method to determine its cytotoxicity. Results As the dosing ratio increased from 80:100 (mass ratio of paclitaxel to poly 2-oxazoline) to 110: 100, the micelles gradually became spherical and became worm-like. The average particle size of the spherical micelles was (43.17 ± 0.95) nm, the entrapment efficiency was (88.81 ± 2.93)% and the drug loading was (40.49 ± 2.03)% at the dosage of 80:100. : 100, the average diameter of the resulting wormlike micelles was (107.83 ± 1.51) nm, the entrapment efficiency was (77.08 ± 0.97)% and the drug loading was (40.34 ± 0.51)%. The cumulative release of spherical and vermicular micelles in phosphate buffered saline for 24 h reached (76.58 ± 3.07)% and (77.66 ± 1.00)%, respectively. The cumulative release was 24 h in PBS with 2% bovine serum albumin The amounts were as high as (100.31 ± 1.80)% and (99.73 ± 2.56)%. The IC50 values of spherical micelles and wormlike micelles on human lung adenocarcinoma A549 cells were 0.336 and 0.342 μg / mL, respectively. Conclusion The spherical and worm-shaped drug-loaded micelles with high loading were prepared successfully. The in vitro cytotoxicity experiments proved that they possess anti-tumor activity.