PEGylation to Improve Protein Stability During Melt Processing.
PEGylation to Improve Protein Stability During Melt Processing.
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DOI：
10.1002/mabi.201500143
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发表时间：
2015-10
影响因子：
4.6
通讯作者：
Pokorski J
中科院分区：
文献类型：
--
作者：
Lee P;Towslee J;Maia J;Pokorski J
生物药品正在迅速增长，是市场上一些最有效的药品，然而，这些药物的交付仍然是一个挑战。熔融处理是一种可行的蛋白质包埋方法，因为它不需要溶剂，产量高，包封率高。然而，有问题的是，由于高热和剪切力，蛋白质在熔融加工过程中可能会变性并失去活性。聚乙二醇的共价连接，通常被称为聚乙二醇化，已被广泛应用于提高蛋白质在水溶液中的热稳定性和防止蛋白质聚集。本研究探讨了聚乙二醇化对溶菌酶和聚乳酸-乙醇酸(PLGA)熔融加工过程中蛋白质稳定性的影响。结果表明，在PLGA熔体加工体系中，聚乙二醇化可以提高溶菌酶后处理的保留活性，增加溶菌酶在熔体中的分散性，降低溶菌酶的两相释放曲线。
Biological pharmaceuticals are growing rapidly and represent some of the most effective pharmaceuticals on the market, however, delivery of these agents remains a challenge. Melt processing is emerging as a viable protein encapsulation method because it is solvent free, is high throughput, and yields very high encapsulation efficiencies. Problematically though, proteins can denature and lose activity during melt processing due to high heat and shear forces. Covalent attachment of poly(ethylene glycol) (PEG), commonly referred to as PEGylation, has been widely used to increase the thermal stability and prevent aggregation of proteins in aqueous solutions. This study explored the effect of PEGylation on protein stability during melt processing using lysozyme and poly(lactic-co-glycolic acid) (PLGA). The results indicate that PEGylation can increase the retained activity of lysozyme post-processing, increase dispersion in the melt, and reduce the biphasic release profile exhibited by lysozyme in PLGA melt processed systems.