| Autor: |
Katz JS; Formulation Science, Core R&D, The Dow Chemical Company, 400 Arcola Road, Collegeville, Pennsylvania 19426, United States., Tan Y; Analytical Sciences, Core R&D, The Dow Chemical Company, 1897 Building, Midland, Michigan 48674, United States., Kuppannan K; Analytical Sciences, Core R&D, The Dow Chemical Company, 1897 Building, Midland, Michigan 48674, United States., Song Y; Department of Chemistry, University of Illinois at Urbana-Champaign, 405 North Matthews Avenue, Urbana, Illinois 61801, United States.; Formulation Science, Core R&D, The Dow Chemical Company, 1712 Building, Midland, Michigan 48674, United States., Brennan DJ; Formulation Science, Core R&D, The Dow Chemical Company, 1712 Building, Midland, Michigan 48674, United States., Young T; Formulation Science, Core R&D, The Dow Chemical Company, 1712 Building, Midland, Michigan 48674, United States., Yao L; Formulation Science, Core R&D, The Dow Chemical Company, 400 Arcola Road, Collegeville, Pennsylvania 19426, United States., Jordan S; Formulation Science, Core R&D, The Dow Chemical Company, 400 Arcola Road, Collegeville, Pennsylvania 19426, United States. |
| Abstrakt: |
With the rapid development of protein-based pharmaceutical products over the past decade, one of the biggest challenges in product development is maintaining the structural stability of proteins during purification, processing, and storage. In this work, the design of a new class of surfactants, polyether-modified N-acyl amino acids, is presented. One surfactant from this series, containing a phenylalanine moiety, demonstrated remarkable stabilization against aggregation of several model protein drugs. Dynamic light scattering, size exclusion chromatography, and circular dichroism all show the rate of thermally accelerated protein aggregation slowed. IgG aggregation was reduced by 3-fold compared to polysorbate controls. Testing of Orencia, a prescription biologic drug for rheumatoid arthritis, demonstrated a 36% improvement in monomer retention upon heat-aging. |
