Journal
JOURNAL OF COLLOID AND INTERFACE SCIENCE
Volume 550, Issue -, Pages 128-138Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.jcis.2019.04.060
Keywords
Monoclonal antibodies; Surfactants; Aggregation; Surface tension; Thin film drainage; Marangoni stresses; Polysorbate; Poloxamer; Polyethylene glycol
Categories
Funding
- Genentech
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Monoclonal antibodies (mAbs) are therapeutic proteins used in the treatment of many diseases due to their specificity in binding targets. Aggregation of these molecules is a major challenge in their formulation development. MAbs spontaneously adsorb onto air-solution interfaces and experience interfacial stresses, which is one of the major causes of aggregation. This work studies the effect of pharmaceutically relevant surfactants like polysorbate-20, poloxamer-188 and polyethylene glycol in controlling the aggregation and interfacial behavior of a mAb prone to interfacial aggregation. Agitation-induced aggregation was characterized using size-exclusion chromatography, flow cytometry and light obscuration. The addition of surfactants reduced the formation of aggregates. In the presence of surfactants competitively adsorbing to the interface, the number of soluble aggregates (size < 100 nm) depended on the amount of mAb adsorbed. On the other hand, the number of insoluble aggregates was governed not by the surface concentration, but by the ability of the adsorbed mAbs to interact and form a cohesive network. To correlate the aggregation in these mAb-surfactant mixtures with their interfacial behavior, studies on the drainage of a fluid film sandwiched between two mAb-surfactant laden interfaces were performed. The amount of fluid entrained depended on different governing mechanisms - interfacial rheology, surface tension and surface tension gradients for different surfactants. The surface tension gradients further resulted in an instability and local thickening in the sandwiched fluid film, which was affected by the presence of mAbs. Understanding the aggregation propensities of different mAb-surfactant mixtures and linking them to the interfacial behavior will greatly aid in understanding the aggregation mechanism and in mitigating aggregate formation by optimizing surfactant type and concentration in the formulation. (C) 2019 Elsevier Inc. All rights reserved.
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