The Effect of Protein PEGylation on Physical Stability in Liquid Formulation

摘要: The presence of micron aggregates in protein formulations has recently attracted increased interest from regulatory authorities, industry, and academia because the potential undesired side effects their presence. In this study, we characterized aggregate formation hen egg-white lysozyme (Lyz) its diPEGylated (5 kDa) analog as a result typical handling stress conditions. Both proteins were subjected to mechanical absence silicone oil (SO), elevated temperatures, freeze-thaw cycles. Flow imaging microscopy showed that PEGylated Lyz formed approximately half many particles Lyz, despite lower apparent thermodynamic stability more loose fold. Further characterization PEGylation led change attractive repulsive protein-protein interactions, which may partly explain reduced particle formation. Surprisingly, adsorbed an order magnitude faster onto SO, being much larger size, determined by small-angle X-ray scattering dynamic light measurements. Thus, significantly reduce, but not prevent, during stresses.