Paper Number
BM13 

Session
Biological Macromolecules: Proteins, Cellulosic Biomass and other Biomaterials

Title
Correlating protein-protein interactions and solution viscosities at high concentration

Presentation Date and Time
October 12, 2015 (Monday) 4:50

Track / Room
Track 4 / Constellation F

Authors (Click on name to view author profile)

1. Woldeyes, Mahlet A. (University of Delaware, Department of Chemical and Biomolecular Engineering)
2. Furst, Eric M. (University of Delaware, Department of Chemical and Biomolecular Engineering)
3. Roberts, Christopher J. (University of Delaware, Department of Chemical and Biomolecular Engineering)

Author and Affiliation Lines (in printed abstract book)
Mahlet A. Woldeyes, Eric M. Furst, and Christopher J. Roberts
Department of Chemical and Biomolecular Engineering, University of Delaware, Newark, DE 19716

Speaker / Presenter 
Woldeyes, Mahlet A.

Text of Abstract
Therapeutic monoclonal antibody (mAb) proteins have the ability to bind tightly and selectively to drug targets. However, high doses are necessary for these proteins to be effective therapeutics. Currently there are two methods of mAb drug administration: intravenous, large volume at dilute condition and subcutaneous, small volume at high concentration. The subcutaneous route is preferred due to its convenience and the possibility of patient self-administration. However, high concentrations lead to undesirable solution behaviors such as increases in viscosity, aggregation, and protein instability.¹

Recent research has attempted to understand the relation between viscosity changes at high protein concentrations with measurements of protein-protein interactions (PPI).² This presentation will focus on work conducted using alpha-chymotrypsinogen A (aCgn) and mAb, where we have experimentally determined the PPI and viscosities over a broad range of protein concentrations. Static and dynamic light scattering were used to measure PPI over a range of ionic strengths and pH conditions. The osmotic second virial coefficient (B₂₂) was used to quantify PPI in dilute regime. Colloidal intermolecular interaction potentials, such as square-well, screened electrostatics, and dipole interactions are used to calculate PPI at dilute protein concentrations. These experimental and modeling results will be presented and the effectiveness of simple colloidal models in predicting PPI from low to high protein concentrations will be discussed. The viscosity of aCgn and mAb solutions was measured using multiple-particle tracking microrheology. The results of these experiments will be presented and discussed in terms of its application in elucidating the connection between PPI and changes in viscosity with increasing protein concentration.

[1] Saluja, A., et al. Int. J. Pharm. 2008, 358 (1-2), 1–15. [2] Neergaard, M. S., et al., Eur. J. Pharm. Sci. 2013, 49 (3), 400–410.