Effects of arginine on the interfacial behavior of proteins

Protein adsorption at fluid-fluid interfaces can induce conformational rearrangements and promote aggregation. Arginine, as an amino acid is known to attenuate protein-protein interactions and lower the viscosity of protein formulations. Given its surface-active properties, we hypothesize that arginine may be effective in limiting aggregation at fluid-fluid interfaces.

Interfacial rheology of Etanercept (Enbrel), Immunoglobulin G1 (IgG1), and Bovine Serum Albumin (BSA) was characterized across a range of concentrations, with and without L-arginine Hydrochloride. The interfacial response was examined in both linear and nonlinear regimes. ζ-potential was also measured for selected formulations to evaluate the relationship between electrostatic characteristics and the rheological outcomes.

Based on both linear and nonlinear interfacial rheology results, arginine generally weakened protein-protein interactions; however, the effect depends on protein identity and concentration. In arginine-containing formulations, Enbrel and BSA displayed only minor variation in interfacial viscoelasticity between 0.01 and 1 mg/mL, particularly during prolonged aging; in contrast, IgG1 showed larger concentration-dependent differences. These results strengthen predictive frameworks for interfacial stability and guide the rational design of protein-amino acid biopharmaceutical formulations.