Protein-polymer conjugation-moving beyond PEGylation.
Protein-polymer conjugation-moving beyond PEGylation.
复制标题
DOI：
10.1016/j.cbpa.2015.08.009
复制
发表时间：
2015-10
影响因子：
7.8
通讯作者：
Chilkoti A
中科院分区：
文献类型：
--
作者：
Qi Y;Chilkoti A
在这篇综述中，我们从材料科学的角度总结了多肽和蛋白质药物的聚合物偶联物领域的现状，重点是作为当前金标准聚乙二醇(PEG)的替代品而开发的聚合物。聚乙二醇化，即聚乙二醇化与生物治疗药物的共价偶联，通过增加其循环半衰期和稳定性来提高其治疗效果，几十年来一直是制药行业的黄金标准。经过多年的研究和开发，聚乙二醇的局限性，特别是其不可降解性和免疫原性越来越明显。尽管聚乙二醇仍是目前临床记录最长的最佳聚合物，但为了解决聚乙二醇的这些局限性，目前正在进行广泛的研究，以开发替代材料。虽然大多数替代材料仍处于早期开发阶段，但它们在体内的分布、降解机制、消除途径和免疫原性还没有得到与聚乙二醇相类似的研究。因此，进一步深入的体内测试对于验证本综述中讨论的任何替代材料是否有资格作为聚乙二醇的替代品是至关重要的。
In this review, we summarize —from a materials science perspective— the current state of the field of polymer conjugates of peptide and protein drugs, with a focus on polymers that have been developed as alternatives to the current gold standard, poly(ethylene glycol) (PEG). PEGylation, or the covalent conjugation of PEG to biological therapeutics to improve their therapeutic efficacy by increasing their circulation half-lives and stability, has been the gold standard in the pharmaceutical industry for several decades. After years of research and development, the limitations of PEG, specifically its non-degradability and immunogenicity have become increasingly apparent. While PEG is still currently the best polymer available with the longest clinical track record, extensive research is underway to develop alternative materials in an effort to address these limitations of PEG. Many of these alternative materials have shown promise, though most of them are still in an early stage of development and their in vivo distribution, mechanism of degradation, route of elimination and immunogenicity have not been investigated to a similar extent as for PEG. Thus, further in-depth in vivo testing is essential to validate whether any of the alternative materials discussed in this review qualify as a replacement for PEG.