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Particle formation during peristaltic pumping of therapeutic proteins : Hofmeister anions effect

Västberg, Amanda LU ; Markova, Natalia LU ; Nilsson, Lars LU ; Nylander, Tommy LU ; Sivakumar, Balasubramanian ; Wahlgren, Marie LU orcid and Elofsson, Ulla (2025) In Journal of Pharmaceutical Sciences 114(4).
Abstract

This study reveals specific ion effects on particle formation during peristaltic pumping of a monoclonal Antibody (Antibody A). For this purpose, three anions in the direct Hofmeister series were selected, ranging from the kosmotropic SO42- to the more neutral Cl- and the chaotropic SCN-. Protein particle formation during peristaltic pumping is described primarily as a surface-driven mechanism. Therefore, the effect of the anions was hypothesised to affect the particle formation with the smallest amount of protein adsorbing and the least particles formed in the presence of SCN-, followed by the highest in SO42-. The alternative hypothesis was that most protein... (More)

This study reveals specific ion effects on particle formation during peristaltic pumping of a monoclonal Antibody (Antibody A). For this purpose, three anions in the direct Hofmeister series were selected, ranging from the kosmotropic SO42- to the more neutral Cl- and the chaotropic SCN-. Protein particle formation during peristaltic pumping is described primarily as a surface-driven mechanism. Therefore, the effect of the anions was hypothesised to affect the particle formation with the smallest amount of protein adsorbing and the least particles formed in the presence of SCN-, followed by the highest in SO42-. The alternative hypothesis was that most protein particles would be formed in SCN- due to the lower intrinsic stability of Antibody A. On the other hand, if none of the factors dominates the particle formation, it would not necessarily follow the Hofmeister series linearly. This was shown to be the case as significantly more particles were formed in the presence of NaCl, which could be explained by the interplay of the protein's intrinsic, colloidal, and interfacial stability. Antibody A had the highest protein adsorption in NaCl and the lowest colloidal stability compared to Na2SO4 or NaSCN, which led to the highest amount of subvisual particles formed during pumping.

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author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Anion effects, Hofmeister series, Monoclonal antibody, Peristaltic pumping, Protein aggregation, Protein particles
in
Journal of Pharmaceutical Sciences
volume
114
issue
4
article number
103700
pages
6 pages
publisher
Elsevier
external identifiers
  • pmid:39954809
  • scopus:85218989769
ISSN
0022-3549
DOI
10.1016/j.xphs.2025.103700
language
English
LU publication?
yes
additional info
Publisher Copyright: © 2025 The Authors
id
c470ff12-47f2-42e8-b48c-3ddf2ac10aa5
date added to LUP
2025-03-16 14:32:46
date last changed
2025-07-07 00:30:16
@article{c470ff12-47f2-42e8-b48c-3ddf2ac10aa5,
  abstract     = {{<p>This study reveals specific ion effects on particle formation during peristaltic pumping of a monoclonal Antibody (Antibody A). For this purpose, three anions in the direct Hofmeister series were selected, ranging from the kosmotropic SO<sub>4</sub><sup>2-</sup> to the more neutral Cl<sup>-</sup> and the chaotropic SCN<sup>-</sup>. Protein particle formation during peristaltic pumping is described primarily as a surface-driven mechanism. Therefore, the effect of the anions was hypothesised to affect the particle formation with the smallest amount of protein adsorbing and the least particles formed in the presence of SCN<sup>-</sup>, followed by the highest in SO<sub>4</sub><sup>2-</sup>. The alternative hypothesis was that most protein particles would be formed in SCN<sup>-</sup> due to the lower intrinsic stability of Antibody A. On the other hand, if none of the factors dominates the particle formation, it would not necessarily follow the Hofmeister series linearly. This was shown to be the case as significantly more particles were formed in the presence of NaCl, which could be explained by the interplay of the protein's intrinsic, colloidal, and interfacial stability. Antibody A had the highest protein adsorption in NaCl and the lowest colloidal stability compared to Na<sub>2</sub>SO<sub>4</sub> or NaSCN, which led to the highest amount of subvisual particles formed during pumping.</p>}},
  author       = {{Västberg, Amanda and Markova, Natalia and Nilsson, Lars and Nylander, Tommy and Sivakumar, Balasubramanian and Wahlgren, Marie and Elofsson, Ulla}},
  issn         = {{0022-3549}},
  keywords     = {{Anion effects; Hofmeister series; Monoclonal antibody; Peristaltic pumping; Protein aggregation; Protein particles}},
  language     = {{eng}},
  number       = {{4}},
  publisher    = {{Elsevier}},
  series       = {{Journal of Pharmaceutical Sciences}},
  title        = {{Particle formation during peristaltic pumping of therapeutic proteins : Hofmeister anions effect}},
  url          = {{http://dx.doi.org/10.1016/j.xphs.2025.103700}},
  doi          = {{10.1016/j.xphs.2025.103700}},
  volume       = {{114}},
  year         = {{2025}},
}