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OALib Journal期刊
ISSN: 2333-9721
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聚(2-乙基-2-噁唑啉)-胆固醇氯甲酸酯修饰盐酸阿霉素脂质体的制备及评价
, PP. 1174-1179
Keywords: 盐酸阿霉素,聚(2-乙基-2-噁唑啉)-胆固醇氯甲酸酯,ph敏感,脂质体
Abstract:
本文评价了两亲性ph敏感聚合物聚(2-乙基-2-噁唑啉)-胆固醇氯甲酸酯[poly(2-ethyl-2-oxazoline)-cholesterylmethylcarbonate,peoz-chmc]的缓冲能力。采用硫酸铵梯度法制备盐酸阿霉素脂质体(doxorubicinhydrochlorideliposomes,dox-l),后插入法制备peoz-chmc和聚乙二醇-二硬脂酰磷脂酰乙醇胺(polyethyleneglycol-distearoylphosphatidylethanolamine,peg-dspe)修饰的盐酸阿霉素脂质体(peoz-dox-l和peg-dox-l),对盐酸阿霉素脂质体的理化性质、体外释放、细胞抑制作用和细胞内定位情况进行评价。结果显示,peoz-chmc对微酸环境有一定的缓冲能力。利用葡聚糖凝胶微柱离心法测定脂质体的包封率为(97.3±1.4)%,动态光散射法测定脂质体的粒径在120nm左右,经peg-dspe和peoz-chmc修饰后脂质体的包封率和粒径均无明显改变。zeta电位分析仪结果显示3种脂质体表面电荷均为负值。通过透析实验考察制剂的体外释药行为,结果表明,在ph7.4的释放介质中,peoz-dox-l释放较为缓慢,而在ph5.0时,peoz-dox-l快速释药,显示出良好的ph敏感性。激光共聚焦实验表明核内体的微酸环境可以促进脂质体发生核内体逃逸,直接释放盐酸阿霉素进入细胞核,而dox-l和peg-dox-l均无此作用。细胞抑制作用结果显示,peoz-dox-l对细胞的抑制作用随ph降低而增强,但ph的降低对peg-dox-l和dox-l的细胞抑制作用没有影响。因此peoz-chmc构建的ph敏感脂质体能克服peg链抑制脂质体的细胞摄取和妨碍ph敏感脂质体的核内体逃逸问题。
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