Research group of Pharmaceutics, School of Pharmacy, Bandung Institute of Technology, Ganesha 10, Bandung 40132, Indonesia.
Biomed Res Int. 2013;2013:943687. doi: 10.1155/2013/943687. Epub 2013 May 2.
We successfully developed recombinant human interferon alpha-2b (rhIFN- α 2b) and mutein forms through the site-directed mutagenesis technique. The mutein forms were developed by substituting cysteins at positions 2 and 99 with aspartic acids. The potential adverse effects of these rhIFN- α 2bs were assessed by acute and subchronic studies.
In the acute study, rhIFN- α 2bs were subcutaneously administered to mice at a single dose of 97.5 μ g/kg, 975 μ g/kg, and 9.75 mg/kg BW and were observed for 14 days. In the subchronic study, single dose of 1.95 μ g/kg and 19.5 μ g/kg, respectively, was given subcutaneously every 3 days for 45 days.
No death as well as abnormality in body weight, behavior, presentation of main organs, and value of plasma SGPT and SGOT was observed. Wild type and mutein rhIFN- α 2bs did not show significant adverse effects at dose up to 9.75 mg/kg BW. Administration of these rhIFN- α 2bs given repeatedly did not induce any adverse effect.
These results suggest that our rhIFN- α 2bs are safe. However, further study is still needed to clarify the safety issue before use in clinical trial.
我们通过定点突变技术成功开发了重组人干扰素 α-2b(rhIFN-α2b)及其突变体。突变体是通过将 2 位和 99 位的半胱氨酸突变为天冬氨酸而开发的。通过急性和亚慢性研究评估了这些 rhIFN-α2b 的潜在不良反应。
在急性研究中，rhIFN-α2b 以 97.5μ g/kg、975μ g/kg 和 9.75mg/kgBW 的单剂量皮下给予小鼠，并观察 14 天。在亚慢性研究中，分别以 1.95μg/kg 和 19.5μg/kg 的剂量，每 3 天皮下给予一次，共 45 天。
未观察到死亡以及体重、行为、主要器官表现、血浆 SGPT 和 SGOT 值的异常。野生型和突变型 rhIFN-α2b 在高达 9.75mg/kgBW 的剂量下未显示出明显的不良反应。反复给予这些 rhIFN-α2b 不会引起任何不良反应。
这些结果表明我们的 rhIFN-α2b 是安全的。然而，在临床试验中使用之前，仍需要进一步研究来澄清安全性问题。
