NGR多肽修饰的9-硝基喜树碱隐形脂质体药剂学性质与抗肿瘤作用研究

目的 考察NGR修饰前后9-硝基喜树碱(9-nitrocamptothecin，9-NC)隐形脂质体的药剂学性质与抗肿瘤作用。方法 采用薄膜-超声化法制备NGR修饰9-NC隐形脂质体，以未经NGR修饰的隐形脂质体作对照，考察包封率、体外释放度、内酯稳定性等药剂学性质；以HT1080为细胞模型，MTT法考察NGR修饰与未修饰9-NC隐形脂质体对细胞生长的影响，流式细胞实验比较NGR修饰与未修饰组的入胞效率。结果 NGR修饰对9-NC隐形脂质体的药剂学性质没有显著影响。修饰后的9-NC隐形脂质体对HT1080细胞的抑制率明显高于未修饰组(P<0.05)，流式细胞实验显示修饰后的脂质体入胞效率显著提高。结论 NGR修饰能够显著提高9-NC隐形脂质体的抗肿瘤效果和入胞效率。

Pharmaceutical Properties and Anti-tumor Study of 9-Nitrocamptothecin Stealth Liposome Modified by NGR Polypeptides

OBJECTIVE To study the pharmaceutical properties and anti-tumor activity of 9-nitrocamptothecin(9-NC) stealth liposome between NGR polypeptides modification and unmodified group. METHODS Liposome was prepared using film-ultrasonic method, and its pharmaceutical properties, such as entrapment efficiency, release in vitro, lactone stability, were compared between modified and unmodified group. Based on HT1080 cells model, MTT method was used to investigate the effect on the growth of cells between NGR modified and unmodified group. Flow cytometry experiments were conducted to compare entry effect between two groups. RESULTS No significant differences were observed between liposome modified by NGR polypeptide and unmodified group in terms of pharmaceutical properties, release degree in vitro, and lactone stability. However, the experimental results showed that inhibition rate of HT1080 cells in the modified 9-NC stealth liposome increased significantly than that in unmodified group(P<0.05). Further, HT1080 uptake rate of NGR-modified liposome was significantly higher than unmodified liposomes. CONCLUSION While from the point of pharmaceutical properties, NGR polypeptides modified liposome show no significant difference, their antitumor effect and uptake efficiency are higher than unmodified group.