ArticleAntioxidants (Basel, Switzerland)2020
Protein Formulations Containing Polysorbates: Are Metal Chelators Needed at All?
Article in Antioxidants (Basel, Switzerland), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
11 citing papers in PubMed, 17 citations in OpenAlex.
- Review
- Article
- From permeation enhancer to therapeutic enabler: Advances, applications, and translational perspectives in hyaluronidase-based drug delivery.Materials today. Bio · 2026Review
- Developing high-concentration monoclonal antibody formulations for subcutaneous administration to improve patient treatment.Biophysical reviews · 2025Review
- How to assess antioxidant activity? Advances, limitations, and applications of in vitro, in vivo, and ex vivo approaches.Food production, processing and nutrition · 2025Review
- Oxidation of polysorbates - An underestimated degradation pathway?International journal of pharmaceutics: X · 2023Review
- Oxidation of Drugs during Drug Product Development: Problems and Solutions.Pharmaceutics · 2022Review
- A Comprehensive Assessment of All-Oleate Polysorbate 80: Free Fatty Acid Particle Formation, Interfacial Protection and Oxidative Degradation.Pharmaceutical research · 2021Article
- The application of pharmaceutical quality by design concepts to evaluate the antioxidant and antimicrobial properties of a preservative system including desferrioxamine.Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences · 2020Article
- Theoretical Study of the Iron Complexes with Aminoguanidine: Investigating Secondary Antioxidant Activity.Antioxidants (Basel, Switzerland) · 2020Article
- Theoretical Study of the Iron Complexes with Lipoic and Dihydrolipoic Acids: Exploring Secondary Antioxidant Activity.Antioxidants (Basel, Switzerland) · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Proteins are prone to post-translational modifications at specific sites, which can affect their physicochemical properties, and consequently also their safety and efficacy. Sources of post-translational modifications include oxygen and reactive oxygen species. Additionally, catalytic amounts of Fe(II) or Cu(I) can promote increased activities of reactive oxygen species, and thus catalyse the production of particularly reactive hydroxyl radicals. When oxidative post-translational modifications are detected in the biopharmaceutical industry, it is common practice to add chelators to the formulation. However, the resultant complexes with metals can be even more damaging. Indeed, this is supported here using an ascorbate redox system assay and peptide mapping. Ethylenediaminetetraacetic acid (EDTA) addition strongly accelerated the formation of hydroxyl radicals in an iron-ascorbate system, while diethylenetriaminepentaacetic acid (DTPA) addition did not. When Fe(III) was substituted with Cu(II), EDTA addition almost stopped hydroxyl radical production, whereas DTPA addition showed continued production, but at a reduced rate. Further, EDTA accelerated metal-catalysed oxidation of proteins, and thus did not protect them from Fe-mediated oxidative damage. As every formulation is unique, justification for EDTA or DTPA addition should be based on experimental data and not common practice.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.