Protein spherulites for sustained release of interferon: preparation, characterization and in vivo evaluation.
Protein spherulites for sustained release of interferon: preparation, characterization and in vivo evaluation.
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DOI：
10.1002/jps.22403
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发表时间：
2011-05
影响因子：
3.8
通讯作者：
Yanbo Jiang;K. Shi;Dengning Xia;Shuo Wang;Tao Song;F. Cui
中科院分区：
文献类型：
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作者：
Yanbo Jiang;K. Shi;Dengning Xia;Shuo Wang;Tao Song;F. Cui
这项研究开发了蛋白质球粒，这是一种新的蛋白质聚集形式，用于重组人干扰素 α-2b (rhIFN) 的缓释应用。在不同的培养温度下，用不同pH值的溶液、不同种类和浓度的锌盐制备rhIFN球晶。不同体系下产生的rhIFN球晶具有不同的形态特性和体外释放特性。尺寸排阻高效液相色谱分析表明球晶形成过程中没有产生蛋白质聚集体，细胞病变抑制实验表明球晶rhIFN很好地保持了其结构和抗病毒活性。体内研究表明，与可溶性rhIFN制剂相比，rhIFN球晶提供了显着延长的药代动力学特征，并且基于血清rhIFN水平的相对生物利用度约为170%。这里描述的工作证明了蛋白质球晶作为 rhIFN 长效制剂的可能性。
This study develops protein spherulite, a new form of protein aggregation, for sustained-release applications of recombinant human interferon α-2b (rhIFN). rhIFN spherulites were prepared with different pH solutions with different kinds and concentrations of zinc salts at various incubation temperatures. rhIFN spherulites produced under different systems were of different morphology properties and in vitro release characters. Size-exclusion high-performance liquid chromatography analysis has shown that no protein aggregates were generated during spherulite formation, and cytopathic inhibition assay has demonstrated that the spherulitic rhIFN well maintained its structure and antiviral activity. In vivo studies showed that rhIFN spherulites provided a significantly prolonged pharmacokinetics profile profile as compared with the soluble rhIFN formulation, and the relative bioavailability based on serum rhIFN levels was about 170%. The work described here demonstrates the possibility of protein spherulites as a long-acting formulation for rhIFN.