甘草次酸修饰的金属有机框架载药系统的研究

Study on Metal-Organic Framework Drug Loading System Modified by Glycyrrhetinic Acid

目的:以金属有机框架材料UiO-66-NH2为载体,以甘草次酸(GA)对其进行表面化学修饰,构建UiO-66- NH2-GA,考察其作为药物载体的载药能力。方法:以一锅法合成载体UiO-66-NH2,在UiO-66-NH2上修饰GA,以浸渍法制备装载5-FU的5-FU@UiO-66-NH2-GA,通过X射线衍射法(XRD)、红外光谱法(IR)、差示扫描量热法(DSC)和扫描电镜(SEM)对UiO-66-NH2-GA及5-FU@UiO-66-NH2-GA的晶型结构及载药性能进行表征,通过MTT实验研究5-FU@UiO-66-NH2-GA的体外抗肿瘤活性。结果:UiO-66-NH2及UiO-66-NH2-GA均为正八面体结构且晶型结构稳定,UiO-66-NH2-GA对5-FU的载药率高达80.9%,5-FU@UiO-66-NH2-GA在pH 5.5的释放介质中比pH 6.5,7.4可以更好地有效释放,5-FU@UiO-66-NH2-GA比5-FU具有更强的抑制肝癌细胞生长的能力。结论:本研究成功制备出具有良好肝靶向性的药物载体UiO-66-NH2-GA,为金属有机框架作为药物载体提供有力的依据。

Objective:The purpose of this study was to formulate and evaluate the metal organic framework modified with glycyrrhetinic acid(UiO-66-NH2-GA).Methods:The metal organic framework(UiO-66-NH2)was prepared via one pad method,and modified by glycyrrhetinic acid.5-FU@UiO-66-NH2-GA was generated by impregnation method.It was characterized by X-ray diffraction(XRD),infrared spectroscopy(IR),differential scanning calorimetry(DSC)and scanning electron micros-copy(SEM).The loading capacity,release capacity,and anticancer effect were also investigated.Results:The characterization experiments indicated that UiO-66-NH2 and UiO-66-NH2-GA were both regular octahedral structure and the crystal structure were stable.The drug loading reached 80.90%.5-FU@UiO-66-NH2-GA showed a higher cumulative release rate at pH 5.5 than that at pH 6.5 and 7.4.The results from MTT suggested that UiO-66-NH2-GA significantly improved the anti-cancer effect of 5-FU.Conclusion:This paper provided a powerful basis for UiO-66-NH2-GA as a good drug carrier.