Viscosity Behavior of High-Concentration Protein Mixtures

Galush, William J.; Le, Lan N.; Moore, Jamie

doi:10.1002/jps.23002

Cited by 39 publications

(29 citation statements)

References 24 publications

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“…Two explanations can be postulated with respect to this observation: decrease in intermolecular interactions and dehydration of the protein core during irradiation. Galush et al, [40] showed that the high viscosity characteristic of high protein concentration solutions is caused by molecular crowding and direct interactions among proteins. Such interactions lead to the formation of long-range protein networks and result in high solution viscosity.…”

Section: Resultsmentioning

confidence: 99%

The secondary structure of proteins in liquid, frozen, and dried egg-white samples: Effect of gamma irradiation treatment

Sarıbay

Ergün

Kalaycı

et al. 2016

International Journal of Food Properties

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In this study, the effect of gamma irradiation treatment on the secondary structure of the whole egg-white proteins was investigated. Liquid, frozen, and dried egg-white samples were subjected to gamma irradiation doses of 0, 1, 2, and 3 kGy. Protein secondary structures were determined by Attenuated Total Reflectance Fourier-Transform Infrared (ATR-FTIR) spectroscopy. In liquid eggwhite samples, irradiation caused a conformational change from α-helix to disordered structure. Besides, a decrease in intermolecular β-sheet content was detected. On the other hand, no significant changes were observed in the secondary structure of frozen and dried egg-white samples. The significance of the results and their possible relationship to the viscosity decrease was also discussed. It was suggested that radiation-induced structural rearrangements may play a key role in the viscosity decrease.

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Section: Resultsmentioning

confidence: 99%

The secondary structure of proteins in liquid, frozen, and dried egg-white samples: Effect of gamma irradiation treatment

Sarıbay

Ergün

Kalaycı

et al. 2016

International Journal of Food Properties

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“…In general, DSF application in the presence of surfactants requires higher protein concentration than in its absence. Fortunately, the current trend in biologics development frequently demands high‐concentration formulations especially for MAbs 24,25. This makes it possible to use SYPRO® Orange dye in surfactant‐containing high‐concentration formulations.…”

Section: Discussionmentioning

confidence: 99%

“…Fortunately, the current trend in biologics development frequently demands high-concentration formulations especially for MAbs. 24,25 This makes it possible to use SYPRO R Orange dye in surfactant-containing high-concentration formulations.…”

Section: Discussion Dsf In the Presence Of Surfactantsmentioning

confidence: 99%

DSF Method Optimization and Its Application in Predicting Protein Thermal Aggregation Kinetics

Shi

Semple

Cheung

et al. 2013

Journal of Pharmaceutical Sciences

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“…This has led to the development of small volume (typically, 1 mL), highly concentrated antibody formulations (typically, 100 mg/mL or more) for delivery via subcutaneous injections. [1][2][3][4][5][6] In our experience, most therapeutic mAb candidates are amenable to such product development, but, in some cases, high solution viscosity can become a hurdle while developing high concentration antibody drug products.…”

Section: Introductionmentioning

confidence: 99%

Rational design of viscosity reducing mutants of a monoclonal antibody: Hydrophobic versus electrostatic inter-molecular interactions

Nichols

Kumar

et al. 2015

mAbs

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High viscosity of monoclonal antibody formulations at concentrations ≥100 mg/mL can impede their development as products suitable for subcutaneous delivery. The effects of hydrophobic and electrostatic intermolecular interactions on the solution behavior of MAB 1, which becomes unacceptably viscous at high concentrations, was studied by testing 5 single point mutants. The mutations were designed to reduce viscosity by disrupting either an aggregation prone region (APR), which also participates in 2 hydrophobic surface patches, or a negatively charged surface patch in the variable region. The disruption of an APR that lies at the interface of light and heavy chain variable domains, VH and VL, via L45K mutation destabilized MAB 1 and abolished antigen binding. However, mutation at the preceding residue (V44K), which also lies in the same APR, increased apparent solubility and reduced viscosity of MAB 1 without sacrificing antigen binding or thermal stability. Neutralizing the negatively charged surface patch (E59Y) also increased apparent solubility and reduced viscosity of MAB 1, but charge reversal at the same position (E59K/R) caused destabilization, decreased solubility and led to difficulties in sample manipulation that precluded their viscosity measurements at high concentrations. Both V44K and E59Y mutations showed similar increase in apparent solubility. However, the viscosity profile of E59Y was considerably better than that of the V44K, providing evidence that inter-molecular interactions in MAB 1 are electrostatically driven. In conclusion, neutralizing negatively charged surface patches may be more beneficial toward reducing viscosity of highly concentrated antibody solutions than charge reversal or aggregation prone motif disruption.

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Viscosity Behavior of High-Concentration Protein Mixtures

Cited by 39 publications

References 24 publications

The secondary structure of proteins in liquid, frozen, and dried egg-white samples: Effect of gamma irradiation treatment

The secondary structure of proteins in liquid, frozen, and dried egg-white samples: Effect of gamma irradiation treatment

DSF Method Optimization and Its Application in Predicting Protein Thermal Aggregation Kinetics

Rational design of viscosity reducing mutants of a monoclonal antibody: Hydrophobic versus electrostatic inter-molecular interactions

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