Molecular Flexibility of Antibodies Preserved even in the Dense Phase after Macroscopic Phase Separation
(2021) In Molecular Pharmaceutics 18(11). p.4162-4169- Abstract
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... (More)
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.
(Less)
- author
- publishing date
- 2021-11-01
- type
- Contribution to journal
- publication status
- published
- keywords
- antibody therapy, diffusion, dynamics, molecular flexibility
- in
- Molecular Pharmaceutics
- volume
- 18
- issue
- 11
- pages
- 8 pages
- publisher
- The American Chemical Society (ACS)
- external identifiers
-
- pmid:34637319
- scopus:85118114235
- ISSN
- 1543-8384
- DOI
- 10.1021/acs.molpharmaceut.1c00555
- language
- English
- LU publication?
- no
- id
- 7f6102b4-446f-49ac-9255-0566c6706c90
- date added to LUP
- 2023-08-14 10:27:56
- date last changed
- 2024-04-20 00:30:47
@article{7f6102b4-446f-49ac-9255-0566c6706c90, abstract = {{<p>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.</p>}}, author = {{Girelli, Anita and Beck, Christian and Bäuerle, Famke and Matsarskaia, Olga and Maier, Ralph and Zhang, Fajun and Wu, Baohu and Lang, Christian and Czakkel, Orsolya and Seydel, Tilo and Schreiber, Frank and Roosen-Runge, Felix}}, issn = {{1543-8384}}, keywords = {{antibody therapy; diffusion; dynamics; molecular flexibility}}, language = {{eng}}, month = {{11}}, number = {{11}}, pages = {{4162--4169}}, publisher = {{The American Chemical Society (ACS)}}, series = {{Molecular Pharmaceutics}}, title = {{Molecular Flexibility of Antibodies Preserved even in the Dense Phase after Macroscopic Phase Separation}}, url = {{http://dx.doi.org/10.1021/acs.molpharmaceut.1c00555}}, doi = {{10.1021/acs.molpharmaceut.1c00555}}, volume = {{18}}, year = {{2021}}, }