Paper Number
BF8 

Session
Biomaterials and Bio-fluid Dynamics

Title
Polysorbate identity and content dictates the extensional flow properties of protein-excipient solutions

Presentation Date and Time
October 11, 2022 (Tuesday) 10:10

Track / Room
Track 4 / Michigan AB

Authors (Click on name to view author profile)

1. Lauser, Kathleen T. (University of Minnesota, Chemical Engineering and Materials Science)
2. Rueter, Amy (University of Minnesota, Chemical Engineering and Materials Science)
3. Calabrese, Michelle A. (University of Minnesota, Chemical Engineering and Materials Science)

Author and Affiliation Lines (in printed abstract book)
Kathleen T. Lauser, Amy Rueter and Michelle A. Calabrese
Chemical Engineering and Materials Science, University of Minnesota, Minneapolis, MN 55455

Speaker / Presenter 
Lauser, Kathleen T.

Keywords
experimental methods; bio-fluids; biomaterials; surfactants

Text of Abstract
While protein medications like antibodies are promising for treatment of cancer or autoimmune diseases, significant challenges persist in the development and delivery of high concentration formulations. When these medications are injected, proteins and excipients, added to stabilize against shear, experience extensional deformations that can affect structure and function. Here, we use dripping-onto-substrate (DoS) extensional rheology to examine the extensional flow properties of model ovalbumin protein (OVA) solutions with commonly used FDA-approved excipients– polysorbate 20 and 80 (PS20 and PS80). Despite similarities in polysorbate structures, pronounced differences in the extensional flow behavior are observed for OVA solutions containing PS20 vs. PS80 due to differences in molecular weight, surface tension, and binding affinity with proteins and interfaces^1,2. For moderate protein concentrations (~100 mg/ml), higher surface tensions and faster breakup times are observed in P80 solutions due to inertiocapillary surface-driven flow. As little as 1 mg/mL polysorbate is required to observe these differences. However in ultra-high concentration formulations (>200 mg/mL), undesirable elasticity is observed near the end of thinning. Interestingly, higher solution concentrations are required to observe these weakly elastic effects in polysorbate-containing solutions vs. solutions containing higher molecular weight polymeric excipients like P188¹. Understanding the difference between excipient behavior in extensional flow can help formulate protein medications with greater shelf stability and higher tolerance to adverse flow effects.
1.Lauser, Kathleen T., Amy L. Rueter, and Michelle A. Calabrese. "Small-volume extensional rheology of concentrated protein and protein-excipient solutions." Soft Matter 17.42 (2021): 9624-9635.
2.Lee, Hyo Jin, et al. "Molecular origins of surfactant-mediated stabilization of protein drugs." Advanced drug delivery reviews 63.13 (2011): 1160-1171.