| 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24 h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24 h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。 |
| 关键词: 紫杉醇 聚2-噁唑啉 球形胶束 蠕虫状胶束 |
| DOI：10.16781/j.0258-879x.2017.02.0155 |
| 投稿时间：2016-10-10修订日期：2016-11-25 |
| 基金项目:国家“重大新药创制”专项（2013ZX09J13109-04B）. |
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| Study of morphological changes of poly(2-oxazoline) micelles induced by high loading of drugs |
| XU Min1,ZOU Hao1,GAO Jing1,2* |
(1. Department of Pharmaceutical Science, School of Pharmacy, Second Military Medical University, Shanghai 200433, China;
2. Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing 100850, China
*Corresponding author) |
| Abstract: |
| Objective To prepare the paclitaxel-loaded poly(2-oxazolyl) nano-micelles and to investigate the morphological changes of nano-micelles after changing drug dosage, so as to establish a novel block copolymer micelles delivery system with high loading capacity. Methods The paclitaxel-loaded poly(2-oxazolyl) nano-micelles 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 80:100 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 micelles 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 micelles 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. |
| Key words: paclitaxel poly(2-oxazoline) spherical micelle worm-like micelle |
