(460i) Translational and Rotational Diffusion of Nanoparticles in Hyaluronic Acid Solutions

Understanding the transport of nanoparticles in complex biological environments would inform their design and evaluation for treatment and diagnosis of disease. In this context, the Stokes−Einstein (SE) relation can used to describe the translational and rotational diffusion of small spherical particles in simple Newtonian fluids, but may fail under certain conditions for nanoparticles. Recent experiments have shown deviations from the predictions of the SE relation for the diffusivity of nanoparticles in complex fluids, including polymer melts and polymer solutions. However, deviations from the predictions of the SE relation for nanoparticles in biological fluids have received less attention. Here we report measurements of the translational and rotational diffusion of spherical, polymer grafted nanoparticles in hyaluronic acid solutions spanning the dilute to semi dilute regime.

Hyaluronic acid is an important component of the extracellular matrix and of biological fluids, such as synovium. Nanoparticles used in the study had hydrodynamic diameters of 40 nm and 240 nm and consisted of magnetic cobalt ferrite inorganic cores, either coated with a grafted brush of poly(ethylene glycol) or aggregated as clusters and coated with a block copolymer of poly(lactic acid)-b-poly(ethylene glycol). The cobalt ferrite nanoparticles were such that they possessed a permanent dipole moment and experiences a torque when a magnetic field is applied. The HA solutions were made with varying concentrations of HA of 1.15 MDa molecular weight. The rotational diffusivity of the nanoparticles was examined through dynamic magnetic susceptibility measurements, where the rotational diffusivity is extracted from the frequency response of the nanoparticles in an oscillating magnetic field. The translational diffusivity of the nanoparticles was studied using X-ray photon correlation spectroscopy (XPCS) at the 8-ID-I beamline at the Argonne Advanced Photon Source. These measurements indicated that both the translational and rotational diffusivity of the nanoparticles was much higher in the HA solutions than expected based on the SE relation and for viscosity matched glycerol/water solutions. Interestingly, the ratio of the rotational and translational diffusivities of the nanoparticles obtained by these two methods was found to be constant and largely independent of the concentration of HA in solution, suggesting that the nanoparticles experience a “nanoscale viscosity” that is lower than that measured using traditional rheometry for the HA solutions. These observations suggest that rotational and translational diffusion of nanoparticles below ~200 nm in diameter may be unimpeded by the transient network formed by HA molecules in solution.