Competitive Adsorption of Monoclonal Antibodies and Nonionic Surfactants at Solid Hydrophobic Surfaces

Kapp, Sebastian J.; Larsson, Iben; Weert, Marco van de; Cárdenas, Marité; Jørgensen, Lene

doi:10.1002/jps.24265

Cited by 46 publications

(26 citation statements)

References 76 publications

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“…Protein adsorption at the solid/water interface has been studied by a number of groups using techniques such as ellipsometry, fluorescence and quartz crystal microbalance. [11][12][13][14][15][16] These reports provide a useful consensus about the typical ranges observed for the amount of protein adsorbed and its physical state, under well-defined surface and solution conditions.…”

Section: Introductionmentioning

confidence: 89%

“…Although these studies have demonstrated the relevance of adsorption and desorption processes to structural perturbation and solution aggregation, [10][11][12][13][14][15][16] little insight about mAbs within the adsorbed layers have been reported. Neutron reflection (NR) is a powerful tool able to reveal the thickness and composition of multiple adsorbed protein layers.…”

Section: Introductionmentioning

confidence: 99%

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Interfacial Adsorption of Monoclonal Antibody COE-3 at the Solid/Water Interface

Pan

Leyshon

et al. 2017

ACS Appl. Mater. Interfaces

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Spectroscopic ellipsometry (SE) and neutron reflection (NR) data for the adsorption of a monoclonal antibody (mAb, termed COE-3, pI 8.44) at the bare SiO/water interface are compared here to the simulations based on Derjaguin-Landau-Verwey-Overbeek theory. COE-3 adsorption was characterized by an initial rapid increase in the surface-adsorbed amount (Γ) followed by a plateau. Only the initial rate of the increase in Γ was strongly correlated with the bulk concentration (0.002-0.2 mg/mL), with Γ at the plateau being about 2.2 mg/m (pH 5.5). Simulations captured COE-3 adsorption at equilibrium most accurately, the point at which the outgoing flux of molecules within the adsorbed plane matched the adsorption flux. Increasing the buffer pH from 5.5 to 9 increased Γ at equilibrium to ∼3 mg/m (0.02 mg/mL COE-3), revealing a dominant role for lateral repulsion between adsorbed mAb molecules. In contrast, increasing the buffer ionic strength (pH 6) reduced Γ, which was captured by simulations accounting for electrostatic screening by ions, in addition to mAb/SiO attractive forces and lateral repulsion. NR data at the same bulk concentrations corroborated the SE data, albeit with slightly higher Γ due to longer adsorption times for data acquisition; for example, at pH 9, Γ was 3.6 mg/m (0.02 mg/mL COE-3), equivalent to a relatively high volume fraction of 0.5. An adsorbed monolayer with a thickness of 50-52 Å was consistently determined by NR, corresponding to the short axial lengths of fragment antigen-binding and fragment crystallization and implying minimal structural perturbation. Thus, the simulations enabled a mechanistic interpretation of the experimental data of mAb adsorption at the SiO/water interface.

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Section: Introductionmentioning

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Interfacial Adsorption of Monoclonal Antibody COE-3 at the Solid/Water Interface

Pan

Leyshon

et al. 2017

ACS Appl. Mater. Interfaces

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“…Quartz crystal microbalance and total internal reflection fluorescence are useful benchtop methods, but lack the resolution to distinguish between individual adsorbed protein layers and the corresponding molecular orientation relative to the surface. 15,16 This becomes limiting when the intention is to define molecular changes to mAbs that undergo adsorption to an interface followed by partial unfolding revealing hydrophobic (core) residues. Consideration must then be given to pathways involving desorption, protein-protein self-assembly (oligomers), and the formation of soluble aggregates that nucleate sub-visible and visible particles.…”

Section: Introductionmentioning

confidence: 99%

Antibody adsorption on the surface of water studied by neutron reflection

Smith

Holman

et al. 2017

mAbs

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Surface and interfacial adsorption of antibody molecules could cause structural unfolding and desorbed molecules could trigger solution aggregation, resulting in the compromise of physical stability. Although antibody adsorption is important and its relevance to many mechanistic processes has been proposed, few techniques can offer direct structural information about antibody adsorption under different conditions. The main aim of this study was to demonstrate the power of neutron reflection to unravel the amount and structural conformation of the adsorbed antibody layers at the air/water interface with and without surfactant, using a monoclonal antibody 'COE-3 0 as the model. By selecting isotopic contrasts from different ratios of H 2 O and D 2 O, the adsorbed amount, thickness and extent of the immersion of the antibody layer could be determined unambiguously. Upon mixing with the commonly-used non-ionic surfactant Polysorbate 80 (Tween 80), the surfactant in the mixed layer could be distinguished from antibody by using both hydrogenated and deuterated surfactants. Neutron reflection measurements from the co-adsorbed layers in null reflecting water revealed that, although the surfactant started to remove antibody from the surface at 1/100 critical micelle concentration (CMC) of the surfactant, complete removal was not achieved until above 1/10 CMC. The neutron study also revealed that antibody molecules retained their globular structure when either adsorbed by themselves or co-adsorbed with the surfactant under the conditions studied.

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“…Surfactants are generally added in mAbs formulations to reduce the exposure of hydrophobic regions and so decreasing proteinprotein interactions and interface-induced aggregation, also prevented by competition for adsorption sites. 129,130 Frequently used nonionic surfactants in mAb drug formulation are polysorbate 20 and polysorbate 80, 17,83 with poloxamers being a potential alternative. 131 Indeed, polysorbate 80 seems to be one of the most protecting surfactant against mechanical stresseinduced aggregation when compared to some other nonionic and anionic surfactants at the same concentration, 130 and also seems to be less perturbing toward mAb higher structure stability when compared to polysorbate 20.…”

Section: Excipientsmentioning

confidence: 99%

Physicochemical Stability of Monoclonal Antibodies: A Review

Basle

Chennell

Tokhadzé

et al. 2020

Journal of Pharmaceutical Sciences

296

162

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Monoclonal antibodies (mAbs) are subject to instability issues linked to their protein nature. In this work, we review the different mechanisms that can be linked to monoclonal antibodies instability, the parameters, and conditions affecting their stability (protein structure and concentration, temperature, interfaces, light exposure, excipients and contaminants, and agitation) and the different analytical methods used for appropriate physicochemical stability studies: physical stability assays (aggregation, fragmentation, and primary, secondary, and tertiary structure analysis), chemical stability assays and quantitative assays. Finally, data from different published stability studies of mAbs formulations, either in their reconstituted form, or in diluted ready to administer solutions, was compiled. Overall, the physicochemical stability of mAbs is linked to numerous factors such as formulation, environment, and manipulations, and must be thoroughly investigated using several complementary analytical techniques, each of which allowing specific characterization information to be harvested. Several stability studies have been published, some of them showing possibilities of extended stability. However, those data should be questioned due to potential lacks in study methodology.

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Competitive Adsorption of Monoclonal Antibodies and Nonionic Surfactants at Solid Hydrophobic Surfaces

Cited by 46 publications

References 76 publications

Interfacial Adsorption of Monoclonal Antibody COE-3 at the Solid/Water Interface

Interfacial Adsorption of Monoclonal Antibody COE-3 at the Solid/Water Interface

Antibody adsorption on the surface of water studied by neutron reflection

Physicochemical Stability of Monoclonal Antibodies: A Review

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