The browser you are using is not supported by this website. All versions of Internet Explorer are no longer supported, either by us or Microsoft (read more here: https://www.microsoft.com/en-us/microsoft-365/windows/end-of-ie-support).

Please use a modern browser to fully experience our website, such as the newest versions of Edge, Chrome, Firefox or Safari etc.

Photo Mikael Lund

Mikael Lund

Professor

Photo Mikael Lund

Chemometrics in Protein Formulation : Stability Governed by Repulsion and Protein Unfolding

Author

  • Alina Kulakova
  • Dillen Augustijn
  • Inas El Bialy
  • Lorenzo Gentiluomo
  • Maria Laura Greco
  • Stefan Hervø-Hansen
  • Sowmya Indrakumar
  • Sujata Mahapatra
  • Marcello Martinez Morales
  • Christin Pohl
  • Marco Polimeni
  • Aisling Roche
  • Hristo L. Svilenov
  • Andreas Tosstorff
  • Matja Zalar
  • Robin Curtis
  • Jeremy P. Derrick
  • Wolfgang Frieß
  • Alexander P. Golovanov
  • Mikael Lund
  • Allan Nørgaard
  • Tarik A. Khan
  • Günther H.J. Peters
  • Alain Pluen
  • Dierk Roessner
  • Werner W. Streicher
  • Christopher F. van der Walle
  • Jim Warwicker
  • Shahid Uddin
  • Gerhard Winter
  • Jens Thostrup Bukrinski
  • Åsmund Rinnan
  • Pernille Harris
Show all

Summary, in English

Therapeutic proteins can be challenging to develop due to their complexity and the requirement of an acceptable formulation to ensure patient safety and efficacy. To date, there is no universal formulation development strategy that can identify optimal formulation conditions for all types of proteins in a fast and reliable manner. In this work, high-throughput characterization, employing a toolbox of five techniques, was performed on 14 structurally different proteins formulated in 6 different buffer conditions and in the presence of 4 different excipients. Multivariate data analysis and chemometrics were used to analyze the data in an unbiased way. First, observed changes in stability were primarily determined by the individual protein. Second, pH and ionic strength are the two most important factors determining the physical stability of proteins, where there exists a significant statistical interaction between protein and pH/ionic strength. Additionally, we developed prediction methods by partial least-squares regression. Colloidal stability indicators are important for prediction of real-time stability, while conformational stability indicators are important for prediction of stability under accelerated stress conditions at 40 °C. In order to predict real-time storage stability, protein-protein repulsion and the initial monomer fraction are the most important properties to monitor.

Department/s

  • Computational Chemistry
  • LTH Profile Area: Nanoscience and Semiconductor Technology
  • Physical Chemistry
  • eSSENCE: The e-Science Collaboration

Publishing year

2023-06

Language

English

Pages

2951-2965

Publication/Series

Molecular Pharmaceutics

Volume

20

Issue

6

Document type

Journal article

Publisher

The American Chemical Society (ACS)

Topic

  • Biological Sciences
  • Biophysics
  • Physical Chemistry (including Surface- and Colloid Chemistry)

Keywords

  • colloidal and conformational stability
  • multivariate data analysis
  • protein characterization
  • protein formulation
  • therapeutic proteins

Status

Published

ISBN/ISSN/Other

  • ISSN: 1543-8384