Paper Number
PO131 

Session
Poster Session

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

Presentation Date and Time
October 8, 2014 (Wednesday) 6:05

Track / Room
Poster Session / Poster

Authors (Click on name to view author profile)

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

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

Speaker / Presenter 
Woldeyes, Mahlet A.

Text of Abstract

Therapeutic monoclonal antibodies are effective due to their ability to bind tightly and selectively to the drug targets. However, high doses are necessary for the effectiveness of these proteins. Currently there are two methods of drug administration; intravenous, large volume at dilute condition and subcutaneous, small volume at high concentration.[1] The subcutaneous route of drug administration 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.[2] Improved understanding the cause of such undesirable behaviors may lead to new strategies to alleviate current difficulties when formulating and manufacturing mAb products.

Recent research has attempted to understand the relation between viscosity changes at high concentrations with measurements of protein-protein interactions (PPI).[3] This poster will focus on initial work conducted using alpha-chymotrypsinogen A (aCgn), where we have experimentally determined PPI and viscosity over a broad range of protein concentration. Static and dynamic light scattering (SLS and DLS), were used to measure PPI over a range of ionic strengths and pH conditions. The osmotic second virial coefficient (B₂₂) and the Kirkwood-Buff integral (G₂₂) were used to quantify PPI in dilute and concentrated regimes, respectively. Viscosity of aCgn 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 pronounced increases in viscosity that are sometimes observed at intermediate to high protein concentrations.

[1] S.J. Shire, et al., J. Pharm. Sci. 93, 2004

[2] A. Saluja, et al., Int. J. Pharm. 358, 2008

[3] M.S. Neergaard, et al., Eur. J. Pharm. Sci. 49, 2013