Interfacial Pressure and Viscoelasticity of Antibodies and Their Correlation to Long-Term Stability in Formulation

Pham, Kiet G.; Thompson, Benjamin R.; Wang, Tingting; Samaddar, Shayak; Qian, Ken K.; Liu, Yun; Wagner, Norman J.

doi:10.1021/acs.jpcb.3c05900

Cited by 2 publications

(3 citation statements)

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“…The rheological measurements of the protein molecules at long aging times are lower than what has been reported by the Furst and Wagner groups and are due to the upper limit that can be measured by our technique. 30,31 Thus, while the use of microscopic probes provides a great advantage over the techniques reported earlier in terms of detecting the initial stages in the evolution, either an active microrheology technique or rheometers with larger probes (like the ones used by Pham et al and Wood et al) would be needed to measure the moduli at longer times. 30,31 Furthermore, this passive microrheology technique is capable of not only measuring the average surface viscosity but also detecting local heterogeneities in the interfacial gel.…”

Section: Nist Mab Solutions In Pbs Buffermentioning

confidence: 99%

“…studied the response to the application of shear stress to a mAb film formed at the air–water interface and showed that the protein film formed a soft glass at the air–water interface . More recently, Pham et al also correlated the rheology of industrially relevant mAbs to their long-term stability under storage conditions . However, most of these rheological studies characterized the film after film formation, not during protein adsorption and film formation.…”

Section: Introductionmentioning

confidence: 99%

“…30 More recently, Pham et al also correlated the rheology of industrially relevant mAbs to their long-term stability under storage conditions. 31 However, most of these rheological studies characterized the film after film formation, not during protein adsorption and film formation. As a result, details of the change in interfacial rheology, as the protein molecules adsorb to the air−water interface, currently remain unknown.…”

Section: Introductionmentioning

confidence: 99%

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Using Passive Microrheology to Measure the Evolution of the Rheological Properties of NIST mAb Formulations during Adsorption to the Air–Water Interface

Escobar,

Vaclaw,

Lozenski

et al. 2024

Langmuir

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The development of novel protein-based therapeutics, such as monoclonal antibodies (mAbs), is often limited due to challenges associated with maintaining the stability of these formulations during manufacturing, storage, and clinical administration. An undesirable consequence of the instability of protein therapeutics is the formation of protein particles. MAbs can adsorb to interfaces and have the potential to undergo partial unfolding as well as to form viscoelastic gels. Further, the viscoelastic properties may be correlated with their aggregation potential. In this work, a passive microrheology technique was used to correlate the evolution of surface adsorption with the evolution of surface rheology of the National Institute of Standards and Technology (NIST) mAb reference material (NIST mAb) and interface-induced subvisible protein particle formation. The evolution of the surface adsorption and interfacial shear rheological properties of the NIST mAb was recorded in four formulation conditions: two different buffers (histidine vs phosphate-buffered saline) and two different pHs (6.0 and 7.6). Our results together demonstrate the existence of multiple stages for both surface adsorption and surface rheology, characterized by an induction period that appears to be purely viscous, followed by a sharp increase in protein molecules at the interface when the film rheology is viscoelastic and ultimately a slowdown in the surface adsorption that corresponds to the formation of solid-like or glassy films at the interface. When the transitions between the different stages occurred, they were dependent on the buffer/pH of the formulations. The onset of these transitions can also be correlated to the number of protein particles formed at the interface. Finally, the addition of polysorbate 80, an FDA-approved surfactant used to mitigate protein particle formation, led to the interface being surfactant-dominated, and the resulting interface remained purely viscous.

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Section: Nist Mab Solutions In Pbs Buffermentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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