Notorious but not understood: How liquid-air interfacial stress triggers protein aggregation

Publication date: 15 February 2018 Source:International Journal of Pharmaceutics, Volume 537, Issues 1–2 Author(s): Ellen Koepf, Simon Eisele, Rudolf Schroeder, Gerald Brezesinski, Wolfgang Friess 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 ...
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research