title: Characterization of antibody-polyol interactions by static light scattering: implications for physical stability of protein formulations.
abstract: In this study, the nature of interactions between monoclonal antibodies and polyols was studied using static light scattering. Solutions of mAb-U and mAb-P (4-12 mg/mL) were analyzed using static light scattering in buffer, 10% w/v trehalose and ethylene glycol solutions at pH 5.0, 7.0 and 9.0. Mechanical stress studies were conducted by shaking the mAb-U solutions (5mg/mL, pH 5.0, 7.0 and 9.0) and mAb-P solutions (5mg/mL, pH 7.0) at 200 rpm for 5 days at 25°C. Addition of trehalose and ethylene glycol resulted in a decrease in the attractive interactions between mAb-U molecules at pH 7.0 and 9.0, and at pH 9.0 between mAb-P molecules. At a higher ionic strength (300 mM, pH 5.0) trehalose and ethylene glycol decreased attractive interactions for both mAbs. Mechanical stress studies showed higher aggregation of mAb-U in trehalose solutions than ethylene glycol and buffer solutions at pH 7.0 and 9.0. A converse trend was seen for mAb-P at pH 7.0. This study showed that polyols, conformational stabilizers or destabilizers, decrease attractive interactions between protein molecules. The decrease is a result of masking of the hydrophobic sites on a protein as polyols can have favorable hydrophobic interactions with the surface exposed hydrophobic groups.
authors.affiliation: Department of Pharmaceutical Sciences, University of Connecticut, Storrs, CT 06269, United States.
authors.forename: Shermeen A
authors.initials: SA
authors.lastname: Abbas
authors.forename: Vikas K
authors.initials: VK
authors.lastname: Sharma
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Patapoff
authors.forename: Devendra S
authors.initials: DS
authors.lastname: Kalonia
mesh_terms: D000911:Antibodies, Monoclonal / Q000737:chemistry*; D019855:Ethylene Glycol / Q000737:chemistry*; D005079:Excipients / Q000737:chemistry*; D005990:Glycerol / Q000737:chemistry; D057927:Hydrophobic and Hydrophilic Interactions; D008027:Light; D009994:Osmolar Concentration; D055550:Protein Stability; D012542:Scattering, Radiation; D012995:Solubility; D013314:Stress, Mechanical; D013395:Sucrose / Q000737:chemistry; D013997:Time Factors; D014199:Trehalose / Q000737:chemistry*
chemical_list: D000911:Antibodies, Monoclonal; D005079:Excipients; D013395:Sucrose; D014199:Trehalose; D019855:Ethylene Glycol; D005990:Glycerol