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Chemical denaturation as a tool in the formulation optimization of biologics
Open accessAbstract
Biologics have become the fastest growing segment in the pharmaceutical industry. As is the case with all proteins, biologics are susceptible to denature or to aggregate; conditions that, if present, preclude their use as pharmaceuticals. Identifying the solvent conditions that maximize their structural stability is crucial during development. Since the structural stability of a protein is susceptible to different chemical and physical conditions, the use of several complementary techniques can be expected to provide the best answers. Stability measurements that rely on temperature or chemical [urea or guanidine hydrochloride (GuHCl)] denaturation have been the preferred ones in research laboratories and together provide a thorough evaluation of protein stability. In this review, we will discuss chemical denaturation as a tool in the optimization of formulation conditions for biologics, and how chemical denaturation complements the role of thermal denaturation for this purpose.
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“In contrast, high temperatures may also promote particle formation, protein unfolding and aggregation [62, 63].”
From Mechanisms of sterile inflammation after intravitreal injection of antiangiogenic drugs: a narrative review (2021) · cites this paper as [63]
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Cited by
A guide to studying protein aggregation
Housmans, J. A. J., Wu, G., Schymkowitz, J. W. H., & Rousseau, F. (2021) · FEBS Journal · doi:10.1111/febs.16312 · Cited by 231
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Metadata
- Authors
- Freire, E., Schön, A., Hutchins, B. M., & Brown, R. K.
- Corresponding author
- Brown, Richard K.
- Venue
- Drug Discovery Today
- Publisher
- Elsevier BV
- Published
- 2013-10
- Volume
- 18
- Issue
- 19-20
- Pages
- 1007-1013
- ISSN
- 1359-6446 (ISSN-L)
- PMC
- PMC3809824
- OpenAlex
- W1980671580
- Cited by
- 66
- References
- 31
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 7 · 2023: 5 · 2022: 3 · 2021: 11 · 2020: 5 · 2019: 3 · 2018: 8 · 2017: 6 · 2016: 4 · 2015: 3 · 2014: 1 · 2013: 2
- FWCI
- 0.31
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Drug Discovery Today (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute of General Medical Sciences (R44GM096751, R43GM096751)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein purification and stability
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Life Sciences › Immunology and Microbiology › Immunology › Biosimilars and Bioanalytical Methods
- Keywords
- chemical denaturation, protein stability, biologics, formulation optimization, urea denaturation, guanidine hydrochloride, thermal denaturation, protein aggregation
- MeSH terms
- Animals, Biological Products, Chemistry, Pharmaceutical, Humans, Protein Denaturation
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
