Sample Environment: Soft Matter Sample Environment for Small‐Angle Neutron Scattering and Neutron Reflectometry

Lindner, Peter; Schweins, Ralf; Campbell, Richard A.

doi:10.1002/9780470933886.ch14

Cited by 8 publications

(10 citation statements)

References 42 publications

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“…106,107 The term P(q) is referred to as the particle form factor, determined by the protein shape. 108,107 The structure factor S(q) (details in refs 109−111) characterize the interactions between particles in solution. S(q → 0) can be expanded into a series of virial coefficients A n…”

Section: Small-angle Neutronmentioning

confidence: 99%

Biophysical Determinants for the Viscosity of Concentrated Monoclonal Antibody Solutions

Mosca,

Pounot,

Beck

et al. 2023

Mol. Pharmaceutics

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Monoclonal antibodies (mAbs) are particularly relevant for therapeutics due to their high specificity and versatility, and mAb-based drugs are hence used to treat numerous diseases. The increased patient compliance of self-administration motivates the formulation of products for subcutaneous (SC) administration. The associated challenge is to formulate highly concentrated antibody solutions to achieve a significant therapeutic effect, while limiting their viscosity and preserving their physicochemical stability. Protein−protein interactions (PPIs) are in fact the root cause of several potential problems concerning the stability, manufacturability, and delivery of a drug product. The understanding of macroscopic viscosity requires an in-depth knowledge on protein diffusion, PPIs, and self-association/aggregation. Here, we study the self-diffusion of different mAbs of the IgG1 subtype in aqueous solution as a function of the concentration and temperature by quasi-elastic neutron scattering (QENS). QENS allows us to probe the short-time self-diffusion of the molecules and therefore to determine the hydrodynamic mAb cluster size and to gain information on the internal mAb dynamics. Small-angle neutron scattering (SANS) is jointly employed to probe structural details and to understand the nature and intensity of PPIs. Complementary information is provided by molecular dynamics (MD) simulations and viscometry, thus obtaining a comprehensive picture of mAb diffusion.

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Section: Small-angle Neutronmentioning

confidence: 99%

Biophysical Determinants for the Viscosity of Concentrated Monoclonal Antibody Solutions

Mosca,

Pounot,

Beck

et al. 2023

Mol. Pharmaceutics

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“…The pair-distance distribution, p(r) , showed a D max in the range of 50 Å to 55 Å and a shape with a significant shoulder at around 15 Å, a dip at around 20 Å and then a peak at around 30Å (Figure S1C). This shape and its modulation is classic for core-shell particles (Arleth, 1997; Lindner & Zemb, 2002). The values for the radius of gyration, R g is at around 30 Å but due to the inner structure of the particles the value cannot be interpreted as directly as for homogenous particles, and it was not used in the further analysis.…”

Section: Resultsmentioning

confidence: 97%

“…Indeed, we found that mPD5 self-assembled and eluted at ~14.2 mL, independent of initial concentration, whereas PD5, lacking the myristoyl acid, eluted at ~21 mL (Figure 1C). To investigate this further, we used Small Angle X-ray Scattering (SAXS), which has earlier been used to investigate micelle structures of detergents (Lindner & Zemb, 2002) to reveal if mPD5 self-assemble into micellar structures and to determine the micelle structure and size. The obtained SAXS data (Figure 1D and S1) were indeed characteristic for core-shell micellar particles.…”

Section: Resultsmentioning

confidence: 99%

mPD5, a peripherally restricted PICK1 inhibitor for treating chronic pain

Jensen,

Chistensen,

Goddard

et al. 2023

Preprint

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Chronic pain is a complex, debilitating, and escalating health problem worldwide, impacting one in five adults. Current treatment is compromised by dose-limiting side effects including high abuse liability, loss of ability to function socially and professionally, fatigue, drowsiness, and apathy. PICK1 has emerged as a promising target for the treatment of chronic pain conditions. Here, we develop and characterize a cell-permeable fatty acid conjugated bivalent peptide inhibitor of PICK1 and assess its effects on acute and chronic pain. The myristoylated myr-NPEG4-(HWLKV)2, (mPD5), self-assembles into core-shell micelles that provide favourable pharmacodynamic properties and relieves ongoing and evoked mechanical hypersensitivity, thermal hypersensitivity as well as anxio-depressive symptoms in mouse models of neuropathic and inflammatory pain following subcutaneous administration. No overt no side effects were associated with mPD5 administration, and it has no effect on acute nociception. Finally, neuropathic pain is relieved far into the chronic phase (18 weeks post SNI surgery) and while the effect of a single injection ceases after a few hours, repeated administration provides pain relief lasting up to 20 hours after the last injection.

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“…The structure factor under shear, χ μν (ne) ( q ;γ̇), can be determined experimentally by measuring small-angle X-ray or neutron scattering (abbreviated as “SAXS” or “SANS”, respectively) of a sample under shear. Such measurements, called “Rheo-SAXS” or “Rheo-SANS”, have been applied to rheology of soft materials such as colloidal solutions, polymers, and surfactant systems. The xy -component, χ xy ,μν (ne) ( q ;γ̇), is accessible by the irradiation of the incident beam in parallel to the rotational axis in the case of Taylor–Couette flow, for instance.…”

Section: Results and Discussionmentioning

confidence: 99%

Shear Thinning and Nonlinear Structural Deformation of Ionic Liquids with Long Alkyl Chains Studied by Molecular Dynamics Simulation

Yamaguchi

2019

J. Phys. Chem. B

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Nonequilibrium molecular dynamics (MD) simulation was performed on imidazolium-based ionic liquids of two different alkyl chain lengths, and shear-rate-dependent viscosity was evaluated. Compared with the frequency-dependent linear shear viscosity determined by equilibrium MD simulation, shear thinning occurs at the shear rate several times lower than that predicted by the Cox−Merz rule. The deformation of the structure factor was also evaluated as the function of shear rate. The onset of shear thinning corresponds to that of the nonlinearity in the deformation of the charge-alternation mode in both ionic liquids, which is in harmony with the result of our previous work that the shear relaxation of ionic liquids is mainly coupled to the structural relaxation of the charge-alternation mode. In the presence of the polar−nonpolar domain structure characteristic to ionic liquids with a long alkyl chain, in particular, the nonlinearity in the domain mode begins within the Newtonian regime of shear viscosity.

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Sample Environment: Soft Matter Sample Environment for Small‐Angle Neutron Scattering and Neutron Reflectometry

Cited by 8 publications

References 42 publications

Biophysical Determinants for the Viscosity of Concentrated Monoclonal Antibody Solutions

Biophysical Determinants for the Viscosity of Concentrated Monoclonal Antibody Solutions

mPD5, a peripherally restricted PICK1 inhibitor for treating chronic pain

Shear Thinning and Nonlinear Structural Deformation of Ionic Liquids with Long Alkyl Chains Studied by Molecular Dynamics Simulation

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