Center for Complex Fluids Engineering, Department of Chemical Engineering, Carnegie Mellon University, Pittsburgh, Pennsylvania 15213, United States.
Langmuir. 2010 Dec 7;26(23):18231-8. doi: 10.1021/la102709y. Epub 2010 Nov 10.
Covalent grafting of poly(ethylene glycol) chains to proteins ("PEGylation") is emerging as an effective technique to increase the in vivo circulation time and efficacy of protein drugs. PEGylated protein adsorption at a variety of solid/aqueous interfaces is a critical aspect of their manufacture, storage, and delivery. A special category of block copolymer, PEGylated proteins have one or more water-soluble linear polymer (PEG) blocks and a single globular protein block that each exert distinct intermolecular and surface interaction forces. We report the impact of PEGylation on protein adsorption at the interface between aqueous solutions and solid films of poly(lactide-co-glycolide) (PLG), a moderately hydrophobic and negatively charged polymer. Using the model protein lysozyme with controlled degrees of PEGylation, we employ total internal reflection fluorescence techniques to measure adsorption isotherms, adsorption reversibility, and the extent of surface-induced aggregation. Lysozyme PEGylation reduces the extent of protein adsorption and surface-induced aggregation and increases the reversibility of adsorption compared to the unconjugated protein. Results are interpreted in terms of steric forces among grafted PEG chains and their effects on protein-protein interactions and protein orientation on the surface.
聚乙二醇（PEG）链共价接枝到蛋白质上（“PEGylation”）作为一种增加蛋白质药物体内循环时间和疗效的有效技术正在兴起。PEG 化蛋白质在各种固/水界面上的吸附是其制造、储存和输送的关键方面。作为一种特殊的嵌段共聚物，PEG 化蛋白质具有一个或多个水溶性线性聚合物（PEG）块和一个单一的球状蛋白质块，每个块都发挥着独特的分子间和表面相互作用力。我们报告了 PEGylation 对聚（乳酸-共-乙醇酸）（PLG）固体薄膜和水溶液之间界面上蛋白质吸附的影响，PLG 是一种中等疏水性和带负电荷的聚合物。使用具有受控 PEGylation 程度的模型蛋白溶菌酶，我们采用全内反射荧光技术测量吸附等温线、吸附可逆性和表面诱导聚集的程度。与未共轭的蛋白质相比，溶菌酶 PEGylation 降低了蛋白质的吸附程度和表面诱导聚集的程度，并增加了吸附的可逆性。结果根据接枝 PEG 链之间的空间力及其对蛋白质-蛋白质相互作用和蛋白质在表面上的取向的影响进行解释。
