TY  - JOUR
AU  - Girelli, Anita
AU  - Beck, Christian
AU  - Bäuerle, Famke
AU  - Matsarskaia, Olga
AU  - Maier, Ralph
AU  - Zhang, Fajun
AU  - Wu, Baohu
AU  - Lang, Christian
AU  - Czakkel, Orsolya
AU  - Seydel, Tilo
AU  - Schreiber, Frank
AU  - Roosen-Runge, Felix
TI  - Molecular Flexibility of Antibodies Preserved Even in the Dense Phase after Macroscopic Phase Separation
JO  - Molecular pharmaceutics
VL  - 18
IS  - 11
SN  - 1543-8392
CY  - Washington, DC
PB  - American Chemical Society
M1  - FZJ-2021-03880
SP  - 4162–4169
PY  - 2021
AB  - Antibody therapies are typically based on high-concentration formulations that need to be administered subcutaneously. These conditions induce several challenges, inter alia a viscosity suitable for injection, sufficient solution stability, and preservation of molecular function. To obtain systematic insights into the molecular factors, we study the dynamics on the molecular level under strongly varying solution conditions. In particular, we use solutions of antibodies with poly(ethylene glycol), in which simple cooling from room temperature to freezing temperatures induces a transition from a well-dispersed solution into a phase-separated and macroscopically arrested system. Using quasi-elastic neutron scattering during in situ cooling ramps and in prethermalized measurements, we observe a strong decrease in antibody diffusion, while internal flexibility persists to a significant degree, thus ensuring the movement necessary for the preservation of molecular function. These results are relevant for a more dynamic understanding of antibodies in high-concentration formulations, which affects the formation of transient clusters governing the solution viscosity.
LB  - PUB:(DE-HGF)16
C6  - pmid:34637319
UR  - <Go to ISI:>//WOS:000715212700020
DO  - DOI:10.1021/acs.molpharmaceut.1c00555
UR  - https://juser.fz-juelich.de/record/901872
ER  -