Small-volume extensional rheology of concentrated protein and protein-excipient solutions

Kathleen T. Lauser, Amy L. Rueter, Michelle A. Calabrese

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Limited studies measure extensional rheology in protein solutions due to volume constraints and measurement challenges. We developed a small-volume, dripping-onto-substrate (DoS) extensional rheology device to measure the capillary thinning of protein and protein-excipient solutionsviaDoS for the first time. Ovalbumin (OVA) was used as a model system, examinedviaDoS both with and without excipient poloxamer 188 (P188). Water and dilute OVA break apart rapidly and demonstrate inertiocapillary (IC) thinning behavior, where longer breakup times in OVA can be attributed to lower surface tension. Further increasing OVA content leads to longer breakup times and deviations from IC thinning at the start of thinning, however, no evidence of elastic behavior is observed. P188 more effectively lowers the droplet surface tension than OVA, transitioning from IC behavior in dilute solution to weakly elastic behavior at higher concentrations. Combined protein/excipient formulations act synergistically at low concentrations, where breakup times are identical to those of the individual components despite the higher total concentration. However concentrated protein/excipient formulations exhibit elasticity, where extensional rheology parameters depend on P188 content and total concentration. These findings imply that excipients intended to stabilize proteins in shear flow can cause undesirable behavior in extensional flows like injection.

Original languageEnglish (US)
Pages (from-to)9624-9635
Number of pages12
JournalSoft Matter
Volume17
Issue number42
DOIs
StatePublished - Nov 14 2021

Bibliographical note

Funding Information:
This material is based upon work supported by the National Science Foundation Graduate Research Fellowship under Grant No. CON-75851, project 00074041. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the National Science Foundation. The authors thank the Anton Paar VIP program for the shear rheometer used in this work, and Kristen Lemke and Joseph Vallin for assistance with SDS-PAGE.

Publisher Copyright:
© The Royal Society of Chemistry 2021.

PubMed: MeSH publication types

  • Journal Article

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