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Using Cluster Theory to Calculate the Experimental Structure Factors of Antibody Solutions.
Skar-Gislinge, Nicholas; Camerin, Fabrizio; Stradner, Anna; Zaccarelli, Emanuela; Schurtenberger, Peter.
Afiliación
  • Skar-Gislinge N; Physical Chemistry, Department of Chemistry, Lund University, SE-221 00 Lund, Sweden.
  • Camerin F; Soft Condensed Matter, Debye Institute for Nanomaterials Science, Utrecht University, Princetonplein 5, 3584 CC Utrecht, The Netherlands.
  • Stradner A; Physical Chemistry, Department of Chemistry, Lund University, SE-221 00 Lund, Sweden.
  • Zaccarelli E; LINXS - Lund Institute of Advanced Neutron and X-ray Science, Scheelevägen 19, SE-223 70 Lund, Sweden.
  • Schurtenberger P; Institute for Complex Systems, National Research Council (ISC-CNR), Piazzale Aldo Moro 5, 00185 Rome, Italy.
Mol Pharm ; 20(5): 2738-2753, 2023 05 01.
Article en En | MEDLINE | ID: mdl-37067466
Monoclonal antibody solutions are set to become a major therapeutic tool in the years to come, capable of targeting various diseases by clever design of their antigen binding site. However, the formulation of stable solutions suitable for patient self-administration typically presents challenges, as a result of the increase in viscosity that often occurs at high concentrations. Here, we establish a link between the microscopic molecular details and the resulting properties of an antibody solution through the characterization of clusters, which arise in the presence of self-associating antibodies. In particular, we find that experimental small-angle X-ray scattering data can be interpreted by means of analytical models previously exploited for the study of polymeric and colloidal objects, based on the presence of such clusters. The latter are determined by theoretical calculations and supported by computer simulations of a coarse-grained minimal model, in which antibodies are treated as Y-shaped colloidal molecules and attractive domains are designed as patches. Using the theoretically predicted cluster size distributions, we are able to describe the experimental structure factors over a wide range of concentration and salt conditions. We thus provide microscopic evidence for the well-established fact that the concentration-dependent increase in viscosity is originated by the presence of clusters. Our findings bring new insights on the self-assembly of monoclonal antibodies, which can be exploited for guiding the formulation of stable and effective antibody solutions.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Cloruro de Sodio / Anticuerpos Monoclonales Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Mol Pharm Asunto de la revista: BIOLOGIA MOLECULAR / FARMACIA / FARMACOLOGIA Año: 2023 Tipo del documento: Article País de afiliación: Suecia Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Cloruro de Sodio / Anticuerpos Monoclonales Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Mol Pharm Asunto de la revista: BIOLOGIA MOLECULAR / FARMACIA / FARMACOLOGIA Año: 2023 Tipo del documento: Article País de afiliación: Suecia Pais de publicación: Estados Unidos