Logo Logo
Switch Language to German
Koepf, Ellen; Eisele, Simon; Schröder, Rudolf; Brezesinski, Gerald; Friess, Wolfgang (2018): Notorious but not understood: How liquid-air interfacial stress triggers protein aggregation. In: International Journal of Pharmaceutics, Vol. 537, No. 1-2: pp. 202-212
Full text not available from 'Open Access LMU'.


Protein aggregation is a major challenge in the development of biopharmaceuticals. As the pathways of aggregation are manifold, good understanding of the mechanisms behind is essential. Particularly, the presence of liquid-air interfaces has been identified to trigger the formation of large protein particles. Investigations of two monoclonal antibodies (IgGs) at the liquid-air interface exhibited the formation of a highly compressible film. An inhomogeneous protein distribution across the interface with areas of increased packing density was discovered by Brewster-Angle microscopy. Repeated compression and decompression of the film resulted in a considerable hysteresis and in significantly elevated numbers of particles. Furthermore, the extent and speed of compression directly affected the mechanical properties of the film as well as the number of particles formed. Infrared reflection- absorption spectroscopy did not indicate considerable changes in secondary structure compared to FT-IR spectra in solution. Hence, the IgG remains in a native-like conformation at the interface. Consequently, the physical-chemical methods applied in combination with the newly-designed Mini-trough provided substantial new knowledge of the mechanisms of interface-related protein aggregation and enable testing of different formulations under controlled stress conditions. Pure compression and decompression with a Mini-Trough allows a much more controlled stressing than shaking.