Fast nanoparticle diffusion in synovial fluidand hyaluronic acid solutions6 September 2021, by Thamarasee Jeewandara

Characterization of nanoparticles and synovial fluid.Transmission electron microscopy images of (A) PEG5k-and (B) PEG4.9k-PLA6k–coated nanoparticles. (C) Thecore diameter distribution compared to thehydrodynamic diameter distributions obtained fromdynamic light scattering (DLS). (D) Rheologicalcharacterization of synovial fluid. SAXS characterizationof (E) PEG-coated nanoparticles and (F) compositenanoparticles in water and synovial fluid, withcorresponding signal from bovine synovial fluid. Credit:Science Advances, doi: 10.1126/sciadv.abf8467

Nanoparticles have applications as therapeuticagents for joint diseases such as osteoarthritis. Butthe role of nanoparticle diffusion in synovial fluid orthe fluid inside the joint is incompletely understood.In a new report now published on ScienceAdvances, Mythreyi Unni and a research team inchemical engineering and biomedical engineeringin the U.S. used the Stokes-Einstein relationship todescribe the rotational and translational diffusion ofpolymer-coated nanoparticles in quiescent synovialfluid and hyaluronic acid solutions. The outcomesprovided insight to the diffusive behavior ofpolymer-coated inorganic nanoparticles in complexaggregates of biological environments that aretypically present in the joint.

Nanoparticles in the lab

Nanoparticles are therapeutic and diagnosticagents and researchers seek to understand theirdiffusion in biological fluids—key for clinicalapplications. The particles can be engineered tomonitor and treat osteoarthritis, although their rolesof diffusion in synovial fluids remain to beunderstood. In this work, Unni et al. studied thetranslational and rotational diffusion of colloidal,stableand neutral nanoparticles in bovine synovialfluid and in hyaluronic acid solutions, the latter ofwhich constitutes a major component of synovial fluid in the joint. Particles can transfer in a fluid byconvection and diffusion based on random thermalfluctuations described through their translationaland rotational diffusivity as a function of particleand fluid properties. However, deviations from theStokes-Einstein relations have occurred in suchnanoparticles in solution. Nanoparticle diffusion inbiological and polyelectrolyte solutions aretherefore lacking and this information can form anessential guide to design nanoparticles forbiomedical applications, including therapy anddiagnosis of joint disease. Unni et al. used X-rayphoton correlation spectroscopy measurementsand dynamic magnetic susceptibility measurementsand during the experiments, they ensured thecolloidal stability of nanoparticles by coating themwith polyethylene glycol. The outcomes of the studyprovided insight into the behavior of polymer-coated nanoparticles in biological environments.

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X-ray Photon Correlation Spectroscopy (XPCS) and DMSmeasurements of nanoparticles in synovial fluid.Representative autocorrelation function for (A) PEG-coated and (B) composite nanoparticles in synovial fluid.Correlation between characteristic time and wave vectorused to extract diffusion coefficients from XPCSmeasurements of (C) PEG-coated and (D) compositenanoparticles and their corresponding fit curves. Thescaling of tau versus q is ?2.4 in (C) and ? 2.6 in (D).DMS measurements for (E) PEG-coated and (F)composite nanoparticles in bovine synovial fluid. Errors in(A) and (B) are SD of the delay time averaged. Errors in(C) and (D) are the error associated with characteristictime. Credit: Science Advances, doi:10.1126/sciadv.abf8467

Diffusion of nanoparticles in synovial fluid

Unni et al. used polymer-coated cobalt ferritenanoparticles of different hydrodynamic sizesduring the study. The nanoparticles maintained aninorganic core diameter and a hydrodynamicdiameter, which the team measured using transmission electron microscopy. The researchersused flash nanoprecipitation to prepare largercomposite nanoparticles and studied their rotationaldiffusivities in bovine synovial fluid with rheologicalcharacterization studies. Using small-angle X-ray

scattering measurements, they evaluated thestructure and aggregation state of the nanoparticlesin the synovial fluid. Unni et al. then studied thenanoparticles in synovial fluid using X-ray photoncorrelation spectroscopy, which suggested Brownian diffusion of the particles. When theysubjected the materials to alternating magneticfields, they responded by physical particle rotation,known as Brownian relaxation, which followed the Debye model. Dynamic magnetic susceptibilitymeasurements of the coated nanoparticles insynovial fluid showed how larger substrates weremore substantially restricted in the fluid. The teamnext studied the diffusion of nanoparticles inhyaluronic acid solutions—the major component ofsynovial fluid.

Characterization of HA solutions. Rheologicalcharacterization of HA solutions with (A) 0 M NaCl and(B) 0.15 M NaCl. (C) Specific viscosity of HA solutionswith 0 and 0.15 M NaCl as a function of HAconcentration. (D) SAXS characterization of PEGnanoparticles in HA solution with 0.15 M NaCl at 1 and10 mg/ml. (E) small angle X-ray scattering spectroscopy(SAXS) characterization of composite nanoparticles inHA solution with 0.15 M NaCl at 1 and 10 mg/ml. Credit:Science Advances, doi: 10.1126/sciadv.abf8467

Diffusion of nanoparticles in hyaluronic acidsolutions

The team further used hyaluronic acid andcharacterized them using rheometry and notedapparent Newtonian behavior for solutions withconcentrations below 1 mg/mL. The team thenconducted small-angle scattering X-rayspectroscopy measurements to study the structure

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and aggregation state of nanoparticles in hyaluronicacid solutions and in water. While the compositenanoparticles remained intact in water, the teamnoted broader polydispersity for nanoparticles inhyaluronic solutions. The nanoscale viscosity wasdistinct from the macroscopic low shear viscositydetermined from rheometry. The rotational diffusioncoefficients also differed for the two types ofnanoparticles, where the values for the smallernanoparticles were smaller than those for the largercomposite particles. Based on the behavior of thenanoparticles, the team hypothesized thesurrounding medium viscosity to be much largerthan the solvent viscosity, which aligned with AlbertEinstein's investigations on the theory of Brownianmotion. However, in 1942, physicist Maurice L.Huggins modified Einstein's model to describe theviscosity of polymeric solutions, and the hypothesispresented in this work by Unni et al. agreed withthe modified model.

Nanoparticle translational and rotational diffusivities inHA solutions determined from XPCS and DMSmeasurements and predicted by the Stokes-Einsteinequation. (A) Translational diffusion coefficients for HAsolutions with 0 M NaCl. (B) Rotational diffusioncoefficients for HA solutions with 0 M NaCl. (C)Hydrodynamic radii determined from the ratio of theexperimentally determined translational and rotationaldiffusivities for HA solutions with 0 M NaCl. (D)Translational diffusion coefficients for HA solutions with0.15 M NaCl. (E) Rotational diffusion coefficients for HAsolutions with 0.15 M NaCl. (F) Hydrodynamic radiidetermined from the ratio of the experimentallydetermined translational and rotational diffusivities for HAsolutions with 0.15 M NaCl. Observed agreement with

hydrodynamic radii determined independently from DLSmeasurements suggests that the concentration-dependent diffusivity of the nanoparticles is welldescribed by the functional form of the Stokes-Einsteinrelations. Credit: Science Advances, doi:10.1126/sciadv.abf8467

Nanoscale viscosity experienced by the nanoparticlesdetermined from translational and rotation diffusionmeasurements, compared to macroscopic low shearviscosity. (A) Viscosities determined from translationaldiffusivities and rheometry for nanoparticles in HAsolutions with 0 M NaCl. (B) Viscosities determined fromrotational diffusivities and rheometry for nanoparticles inHA solutions with 0 M NaCl. (C) Viscosities determinedfrom translational diffusivities and rheometry fornanoparticles in HA solutions with 0.15 M NaCl. (D)Viscosities determined from rotational diffusivities andrheometry for nanoparticles in HA solutions with 0.15 MNaCl. (E) Nanoscale viscosity experienced by thenanoparticles determined from the experimentaltranslational and rotational diffusivity measurements andconcentration-dependent viscosity of polymer usingHuggins equation for PEG-coated and compositenanoparticles in HA with 0.15 M NaCl. Error bars tend tobe smaller than markers. Credit: Science Advances, doi:10.1126/sciadv.abf8467

Outlook

In this way, Mythreyi Unni and colleaguespresented a reductionist approach to understandthe transport of nanoparticles in a crowded andconfined joint, by studying the diffusion ofnanoparticles in synovial fluid and in hyaluronic

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acid solutions that typically constitute joint fluid. Thecomposition and rheological properties of the fluidcan vary with age and disease to influencenanoparticle diffusion. Additional studies withnanoparticles of a broader size range and coatingsshould be used to assess the transport ofnanoparticles in porous cartilage and multilayeredsynovium. The team described the diffusioncoefficient of the polymer-coated nanoparticlesusing the Stokes-Einstein relationship and followedthis with descriptions of the viscosity of the mediumusing a model developed by Huggins. The workshowed how the diffusive behavior of polymer-coated nanoparticles in biological fluid and theirconstituents can guide nanoparticle designs inbiomedicine.

More information: Unni M. et al. Fastnanoparticle rotational and translational diffusion insynovial fluid and hyaluronic acid solutions, Science Advances, DOI: 10.1126/sciadv.abf8467

Nance E. et al. A dense poly(ethylene glycol)coating improves penetration of large polymericnanoparticles within brain tissue. ScienceTranslational Medicine,10.1126/scitranslmed.3003594

J Topping, Investigations on the Theory of theBrownian Movement, Physics Bulletin (2015). DOI:10.1088/0031-9112/7/10/012

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Provided by Science X NetworkAPA citation: Fast nanoparticle diffusion in synovial fluid and hyaluronic acid solutions (2021, September6) retrieved 29 October 2021 from https://phys.org/news/2021-09-fast-nanoparticle-diffusion-synovial-fluid.html

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