Differences in Dynamics between Crosslinked and Non‐Crosslinked Hyaluronates Measured by using Fast Field‐Cycling Relaxometry

Ravera, Enrico; Fragai, Marco; Parigi, Giacomo; Luchinat, Claudio

doi:10.1002/cphc.201500446

Cited by 20 publications

(21 citation statements)

References 90 publications

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“…At this stage we wish to clearly state that we do not contradict the power-law theory proposed in References [34,35,36,37]. Nevertheless, we exploited an alternative that is (in our opinion) worthy of consideration [38,39,40,41,42].…”

Section: Methodsmentioning

confidence: 91%

“…This concept is based on a decomposition of the overall spin–lattice relaxation rates originating from 1 H– 1 H dipole–dipole interactions into contributions associated with dynamical processes occurring on considerably different time scales. The concept was proposed in Reference [38] and then used for the analysis of 1 H relaxation data for proteins in solution [39,40], in sediments [41], as well as for polymers [42].…”

Section: Introductionmentioning

confidence: 99%

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Dynamics of Solid Proteins by Means of Nuclear Magnetic Resonance Relaxometry

et al. 2019

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1H Nuclear magnetic resonance (NMR) relaxometry was exploited to investigate the dynamics of solid proteins. The relaxation experiments were performed at 37 °C over a broad frequency range, from approximately 10 kHz to 40 MHz. Two relaxation contributions to the overall 1H spin–lattice relaxation were revealed; they were associated with 1H–1H and 1H–14N magnetic dipole–dipole interactions, respectively. The 1H–1H relaxation contribution was interpreted in terms of three dynamical processes occurring on timescales of 10−6 s, 10−7 s, and 10−8 s, respectively. The 1H–14N relaxation contribution shows quadrupole relaxation enhancement effects. A thorough analysis of the data was performed revealing similarities in the protein dynamics, despite their different structures. Among several parameters characterizing the protein dynamics and structure (e.g., electric field gradient tensor at the position of 14N nuclei), the orientation of the 1H–14N dipole–dipole axis, with respect to the principal axis system of the electric field gradient, was determined, showing that, for lysozyme, it was considerably different than for the other proteins. Moreover, the validity range of a closed form expression describing the 1H–14N relaxation contribution was determined by a comparison with a general approach based on the stochastic Liouville equation.

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Section: Methodsmentioning

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Dynamics of Solid Proteins by Means of Nuclear Magnetic Resonance Relaxometry

et al. 2019

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“…They synthesized crosslinked Hyaluronic Acid NPs (cHANPs) loaded with Gd-DTPA through a microfluidic flow-focusing process, demonstrating the possibility to improve relaxivity through the tunability of crosslink density, mesh size, hydrophilicity, and loading capability and by changing the process parameters [ 30 ]. Indeed, the proper control of the structural properties of polymer-based nanohydrogels affects the water molecules' dynamics resulting in a specific condition in a relaxivity boost [ 36 , 37 ]. This effect is called Hydrodenticity [ 31 ].…”

Section: Gadolinium-based Casmentioning

confidence: 99%

New Strategies in the Design of Paramagnetic CAs

Smeraldo

Netti

Torino

2020

Contrast Media & Molecular Imaging

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Nowadays, magnetic resonance imaging (MRI) is the first diagnostic imaging modality for numerous indications able to provide anatomical information with high spatial resolution through the use of magnetic fields and gradients. Indeed, thanks to the characteristic relaxation time of each tissue, it is possible to distinguish between healthy and pathological ones. However, the need to have brighter images to increase differences and catch important diagnostic details has led to the use of contrast agents (CAs). Among them, Gadolinium-based CAs (Gd-CAs) are routinely used in clinical MRI practice. During these last years, FDA highlighted many risks related to the use of Gd-CAs such as nephrotoxicity, heavy allergic effects, and, recently, about the deposition within the brain. These alerts opened a debate about the opportunity to formulate Gd-CAs in a different way but also to the use of alternative and safer compounds to be administered, such as manganese- (Mn-) based agents. In this review, the physical principle behind the role of relaxivity and the T1 boosting will be described in terms of characteristic correlation times and inner and outer spheres. Then, the recent advances in the entrapment of Gd-CAs within nanostructures will be analyzed in terms of relaxivity boosting obtained without the chemical modification of CAs as approved in the chemical practice. Finally, a critical evaluation of the use of manganese-based CAs will be illustrated as an alternative ion to Gd due to its excellent properties and endogenous elimination pathway.

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“…It is present in the synovial fluid and the extracellular matrix of the cartilage (1) where it naturally occurs as a high-molecular weight (HMW) substance with an average molecular weight (MW) of 6 × 10 6 Da (2). …”

Section: Introductionmentioning

confidence: 99%

“…There are claims that reduction of the MW and concentration of HA that occurs in osteoarthritis (OA) would alter the rheological properties of HA resulting in increased friction and reduced protection of the articular cartilage during mechanical stress (2, 4). Viscosupplementation (VS)—the injection of exogenous HA into the synovial joints—has emerged as a therapeutic approach to restore the viscoelasticity of the synovial fluid in the joint (2). …”

Section: Introductionmentioning

confidence: 99%

Polysaccharides As Viscosupplementation Agents: Structural Molecular Characteristics but Not Rheology Appear Crucial to the Therapeutic Response

2017

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IntroductionMost clinical studies and basic research document viscosupplementation (VS) in terms of effectiveness and safety, but only a few highlight its molecular mechanisms of action. Besides, there is generally focus on hyaluronic acid (HA) as being the most relevant polysaccharide to reach the clinical endpoints, attributing its effect mainly to its unique viscoelastic properties, related to a high-molecular weight and gel formulation. Usually, studies do not approach the possible biological pathways where HA may interfere, and there is a lack of reports on other biocompatible polysaccharides that could be of use in VS.AimWe briefly review the main proposed mechanisms of action of intra-articular hyaluronic acid (IA-HA) treatment and discuss its effectiveness focusing on the role of rheological and intrinsic structural molecular properties of polysaccharides in providing a therapeutic effect.MethodsWe conducted a literature search using PubMed database to find articles dealing with the mechanisms of action of IA-HA treatment and/or emphasizing how the structural properties of the polysaccharide used influenced the clinical outcomes.Discussion/conclusionHA is involved in numerous biochemical interactions that may explain the clinical benefits of VS, most of them resulting from HA–cluster of differentiation 44 receptor interaction. There are other important aspects apart from the molecular size or the colloidal state of the IA-HA involved in VS efficiency that still need to be consolidated. Indeed, it seems that clinical response may be dependent on the intrinsic properties of the polysaccharide, regardless of being HA, rather than to rheology, posing some controversy to previous beliefs.

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Differences in Dynamics between Crosslinked and Non‐Crosslinked Hyaluronates Measured by using Fast Field‐Cycling Relaxometry

Cited by 20 publications

References 90 publications

Dynamics of Solid Proteins by Means of Nuclear Magnetic Resonance Relaxometry

Dynamics of Solid Proteins by Means of Nuclear Magnetic Resonance Relaxometry

New Strategies in the Design of Paramagnetic CAs

Polysaccharides As Viscosupplementation Agents: Structural Molecular Characteristics but Not Rheology Appear Crucial to the Therapeutic Response

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