Lee Parker, Towslee Jenna, Maia João, Pokorski Jonathan
Department of Macromolecular Science and Engineering, Case Western Reserve University, Cleveland, Ohio, 44106, USA.
Macromol Biosci. 2015 Oct;15(10):1332-7. doi: 10.1002/mabi.201500143. Epub 2015 Jun 12.
Biopharmaceuticals are some of the most effective drugs on the market, however, delivery remains a challenge. Melt processing is a viable protein encapsulation method because it is solvent free, is high throughput, and yields very high encapsulation efficiencies. Problematically, proteins can lose activity during melt processing due to high heat and shear forces. Covalent attachment of poly(ethylene glycol), or PEGylation, has been widely used to increase thermal stability and prevent aggregation in solution. This study explored the effect of PEGylation on protein stability during melt processing using lysozyme and PLGA. The results indicate that PEGylation increases the retained activity of lysozyme, increases dispersion in the melt, and reduces the biphasic release profile in melt processed systems.
生物制药是市场上一些最有效的药物，然而，给药仍然是一个挑战。熔融加工是一种可行的蛋白质包封方法，因为它无溶剂、高通量且具有非常高的包封效率。问题在于，由于高温和剪切力，蛋白质在熔融加工过程中可能会失去活性。聚乙二醇的共价连接，即聚乙二醇化，已被广泛用于提高热稳定性并防止溶液中的聚集。本研究使用溶菌酶和聚乳酸-羟基乙酸共聚物（PLGA）探讨了聚乙二醇化对熔融加工过程中蛋白质稳定性的影响。结果表明，聚乙二醇化提高了溶菌酶的保留活性，增加了在熔体中的分散性，并减少了熔融加工系统中的双相释放曲线。
