title: Impact of aggregate formation on the viscosity of protein solutions.
abstract: Gaining knowledge on the stability and viscosity of concentrated therapeutic protein solutions is of great relevance to the pharmaceutical industry. In this work, we borrow key concepts from colloid science to rationalize the impact of aggregate formation on the changes in viscosity of a concentrated monoclonal antibody solution. In particular, we monitor the kinetics of aggregate growth under thermal stress by static and dynamic light scattering, and we follow the rise in solution viscosity by measuring the diffusion coefficient of tracer nanoparticles with dynamic light scattering. Moreover, we characterize aggregate morphology in the frame of the fractal geometry. We show that the curves of the increase in viscosity with time monitored at three different protein concentrations collapse on one single master curve when the reaction profiles are normalized based on an effective volume fraction occupied by the aggregates, which depends on the aggregate size, concentration and morphology. Importantly, we find that the viscosity of an aggregate sample is lower than the viscosity of a monomeric sample of a similar occupied volume fraction due to the polydispersity of the aggregate distribution.
authors.affiliation: Department of Chemistry and Applied Biosciences, ETH Zurich, Switzerland.
authors.forename: Lucrèce
authors.initials: L
authors.lastname: Nicoud
authors.forename: Marco
authors.initials: M
authors.lastname: Lattuada
authors.forename: Andrew
authors.initials: A
authors.lastname: Yates
authors.forename: Massimo
authors.initials: M
authors.lastname: Morbidelli
mesh_terms: D007074:Immunoglobulin G / Q000737:chemistry*; D007700:Kinetics; D010316:Particle Size; D066329:Protein Aggregates; D011485:Protein Binding; D012996:Solutions; D012997:Solvents / Q000737:chemistry; D014783:Viscosity
chemical_list: D007074:Immunoglobulin G; D066329:Protein Aggregates; D012996:Solutions; D012997:Solvents