Paper Number
AB14 

Session
Active and Biological Materials

Title
Effect of excipient addition on the extensional flow of protein solutions

Presentation Date and Time
October 12, 2021 (Tuesday) 11:30

Track / Room
Track 4 / Meeting Room C-D

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. Jones, Isabelle (University of Minnesota, Chemical Engineering and Materials Science)
4. Calabrese, Michelle A. (University of Minnesota, Chemical Engineering and Materials Science)

Author and Affiliation Lines (in printed abstract book)
Kathleen T. Lauser, Amy Rueter, Isabelle Jones and Michelle A. Calabrese
Chemical Engineering and Materials Science, University of Minnesota, Minneapolis, MN 55414

Speaker / Presenter 
Lauser, Kathleen T.

Keywords
experimental methods; biological materials; surfactants

Text of Abstract
With global sales of over $288 billion in 2016, solution-based protein medications represent a sizable portion of the pharmaceutical industry.¹ Subcutaneous injection of these medications exposes proteins to strong shear and extensional forces, which can cause conformational changes such as protein denaturation and aggregation, leading to loss of function.² We developed a dripping-onto-substrate (DoS) instrument³ optimized for small-volume measurements on proteins, to link the spatiotemporal decay of a liquid bridge radius to extensional rheological properties. Our experiments with model albumin proteins have shown that even dilute, low viscosity formulations demonstrate differences in thinning behavior that is distinct from water controls. Additionally, we compared DoS experiments with proteins alone to measurements with added excipients, such as poloxamers and polysorbates, that preferentially diffuse to interfaces and protect proteins structure.⁴ While these excipients have been found to be stabilizing to protein solutions in shear⁴, in extensional flows and at higher concentrations, excipients can lengthen the total time or magnitude of extensional deformation, which can ultimately be destabilizing. This work quantifies the effect of extensional flows on protein behavior both with and without excipients, and identifies optimal ranges of excipients that prevent interface aggregation without introducing additional extensional destabilization.
References: 1. Moorkens, E. et. al. Front Pharmacol,11 (2017) 1-12 2. Bekard, I. et al. Biopolymers, 95 (2011): 733-745. 3. Dinic, J. et al. ACS Macro Lett, 4.7 (2015): 804-808. 4. Lee, H. et. al. Adv. Drug Deliver. Rev. (2011) 1160-1171.