Xi K, Tabata Y, Uno K, Yoshimoto M, Kishida T, Sokawa Y, Ikada Y
Research Center for Biomedical Engineering, Kyoto University, Japan.
Pharm Res. 1996 Dec;13(12):1846-50. doi: 10.1023/a:1016037225728.
The purpose of this study was to actively target interferon (IFN) to the liver through its chemical conjugation with pullulan, a water-soluble polysaccharide with a high affinity for the liver.
Chemical conjugation of IFN with pullulan was achieved by a cyanuric chloride method. Following intravenous injection of the conjugates to mice, their body distribution and the activity of an IFN-induced enzyme, 2', 5'-oligoadenylate (2-5A) synthetase in the liver and other organs, were evaluated.
The cyanuric chloride method enabled us to prepare an IFN-pullulan conjugate that retained approximately 7-9% of the biological activity of IFN. Pullulan conjugation enhanced the liver accumulation of IFN and the retention period with the results being reproducible. When injected intravenously to mice, the IFN-pullulan conjugate enhanced the activity of 2-5A synthetase in the liver. The activity could be induced at IFN doses much lower than those of free IFN injection. In addition, the liver 2-5A synthetase induced by conjugate injection was retained for 3 days, whereas it was lost within the first day for the free IFN-injected mice.
IFN-pullulan conjugation was promising for IFN targeting to the liver with efficient exertion of its antiviral activity therein.
本研究的目的是通过将干扰素（IFN）与支链淀粉化学偶联，将其主动靶向至肝脏，支链淀粉是一种对肝脏具有高亲和力的水溶性多糖。
采用三聚氯氰法实现IFN与支链淀粉的化学偶联。将偶联物静脉注射给小鼠后，评估其体内分布以及肝脏和其他器官中IFN诱导酶2',5'-寡腺苷酸（2-5A）合成酶的活性。
三聚氯氰法使我们能够制备出保留约7-9%IFN生物活性的IFN-支链淀粉偶联物。支链淀粉偶联增强了IFN在肝脏中的蓄积以及滞留时间，结果具有可重复性。当静脉注射给小鼠时，IFN-支链淀粉偶联物增强了肝脏中2-5A合成酶的活性。在比游离IFN注射剂量低得多的IFN剂量下即可诱导该活性。此外，偶联物注射诱导的肝脏2-5A合成酶可保留3天，而游离IFN注射的小鼠在第一天内该酶活性就消失了。
IFN-支链淀粉偶联对于将IFN靶向至肝脏并在其中有效发挥其抗病毒活性具有前景。
