Suppression of liquid-liquid phase separation and aggregation of antibodies by modest pressure application

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dc.contributor.authorFetahaj, Zamira
dc.contributor.authorJaworek, Michel W.
dc.contributor.authorOliva, Rosario
dc.contributor.authorWinter, Roland
dc.date.accessioned2024-02-12T12:11:40Z
dc.date.available2024-02-12T12:11:40Z
dc.date.issued2022-06-27
dc.description.abstractThe high colloidal stability of antibody (immunoglobulin) solutions is important for pharmaceutical applications. Inert cosolutes, excipients, are generally used in therapeutic protein formulations to minimize physical instabilities, such as liquid–liquid phase separation (LLPS), aggregation and precipitation, which are often encountered during manufacturing and storage. Despite their widespread use, a detailed understanding of how excipients modulate the specific protein-protein interactions responsible for these instabilities is still lacking. In this work, we demonstrate the high sensitivity to pressure of globulin condensates as a suitable means to suppress LLPS and subsequent aggregation of concentrated antibody solutions. The addition of excipients has only a minor effect. The high pressure sensitivity observed is due to the fact that these flexible Y-shaped molecules create a considerable amount of void volume in the condensed phase, leading to an overall decrease in the volume of the system upon dissociation of the droplet phase by pressure already at a few tens of to hundred bar. Moreover, we show that immunoglobulin molecules themselves are highly resistant to unfolding under pressure, and can even sustain pressures up to about 6 kbar without conformational changes. This implies that immunoglobulins are resistant to the pressure treatment of foods, such as milk, in high-pressure food-processing technologies, thereby preserving their immunological activity.en
dc.identifier.urihttp://hdl.handle.net/2003/42322
dc.identifier.urihttp://dx.doi.org/10.17877/DE290R-24159
dc.language.isoende
dc.relation.ispartofseriesChemistry - a European journal;28(48)
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/de
dc.subjectAntibodiesen
dc.subjectExcipientsen
dc.subjectHigh pressureen
dc.subjectLiquid-liquid phase separationen
dc.subjectProtein condensatesen
dc.subject.ddc540
dc.subject.rswkAntikörperde
dc.subject.rswkArzneistoffträgerde
dc.subject.rswkFlüssig-Flüssig-Systemde
dc.subject.rswkPhasenumwandlungde
dc.subject.rswkProteinde
dc.titleSuppression of liquid-liquid phase separation and aggregation of antibodies by modest pressure applicationen
dc.typeTextde
dc.type.publicationtypeResearchArticlede
dcterms.accessRightsopen access
eldorado.secondarypublicationtruede
eldorado.secondarypublication.primarycitationZ. Fetahaj, M. W. Jaworek, R. Oliva, R. Winter, Chem. Eur. J. 2022, 28, e202201658.de
eldorado.secondarypublication.primaryidentifierhttps://doi.org/10.1002/chem.202201658de

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