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Predicting the Agitation-Induced Aggregation of Monoclonal Antibodies Using Surface Tensiometry.

Abstract：

:Adsorption of antibody therapeutics to air-liquid interfaces can enhance aggregation, particularly when the solution does not contain protective surfactant or when the surfactant is diluted as occurs during preparation of intravenous infusion bags. The ability to predict an antibody's propensity for interfacially mediated aggregation is particularly useful during product development to ensure the quality, potency, and safety of the therapeutic. To develop a predictive tool, we investigated the surface pressure and surface excess of a panel of 16 antibodies as well as determined their aggregation propensity at the air-liquid interface in an agitation stress model. Our data demonstrated that the initial rate of surface pressure increase upon antibody adsorption to the air-liquid interface strongly predicted the extent of agitation-induced aggregation. Other factors, including the hydrophobicity, equilibrium surface pressure, and interfacial concentration of an antibody, were not adequate predictors of its susceptibility to aggregation. In addition to developing a predictive tool, we extended the interfacial characterization to better understand the mechanisms of antibody aggregation at an air-liquid interface during agitation stress. We believe that the kinetics of antibody rearrangement and conformational change after adsorbing to the interface, leading to the development of attractive antibody-antibody interactions, dictated the extent of aggregation. Overall, our results demonstrate how surface pressure measurements can be implemented as a rapid screening tool for the identification of antibodies with a high propensity to aggregate upon adsorption to an air-liquid interface while also furthering our understanding of interfacially mediated protein aggregation.

journal_name

Mol Pharm

journal_title

Molecular pharmaceutics

authors

Shieh IC,Patel AR

doi

10.1021/acs.molpharmaceut.5b00089

subject

Has Abstract

pub_date

2015-09-08 00:00:00

pages

3184-93

issue

9

eissn

1543-8384

issn

1543-8392

journal_volume

12

pub_type

杂志文章

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