(255h) Translational and Rotational Diffusion of Polymer Grafted Nanoparticles in Synovial Fluid and Hyaluronan Solutions

Authors: 
Unni, M., University of Florida
Rinaldi, C., University of Florida
Maldonado-Camargo, L., University of Florida
Savliwala, S., University of Florida
Partain, B., University of Florida
Narayanan, S., Argonne National Laboratory
Sandy, A., Argonne National Laboratory
Zhang, Q., Argonne National Lab
Dufresne, E. M., Argonne National Lab
Grybos, P., AGH University of Science and Technology
Koziol, A., AGH University of Science and Technology
Maj, P., AGH University of Science and Technology
Szczygiel, R., AGH University of Science and Technology
Allen, K., University of Florida
Polymer grafted nanoparticles have been used extensively as diagnostic and therapeutic agents. In the context of osteoarthritis, a degenerative disease of the articular joint, no disease modifying drug exists to date. While engineered biomaterials addressing this challenge are being widely researched, no systematic study on understanding the transport of nanoparticles in the joint’s synovial fluid has been reported. Various theoretical and experimental work have built a foundation for understanding transport of nanoparticles in polymer solutions; however, detailed understanding of transport of nanoparticles in biological fluids is lacking. Here, we study the translation and rotation of polymer grafted nanoparticles in synovial fluid and in hyaluronic acid (HA) solutions, a major constituent of the synovial fluid.

HA solutions with molecular weight 1,100 kDa at concentrations spanning from the dilute to the semi-dilute regime (with C/C* between 0.4 and 8) were used in the study. Cobalt ferrite particles coated with polyethylene glycol of 5kDa and with PEG5kDa_PDLLA6kDa used in the study had hydrodynamic diameters of 44 nm and 220 nm, respectively. Translational diffusion measurements of the nanoparticles suspended in the moderately flexible biopolymer solutions were performed using x-ray photon correlation spectroscopy measurements. The characteristic time obtained from exponential fits to the autocorrelation function was used to extract the diffusion coefficients. The rotational diffusivity of the nanoparticles in polymer solutions was characterized through dynamic magnetic susceptibility measurements by measuring the rotational response of the polymer coated particles to an oscillating magnetic field as a function of frequency.

Experiments using viscosity-matched glycerol solutions showed excellent agreement between measured rotational and translational viscosities and Stokes-Einstein (SE) predictions using macroscopic viscosity measurements. However, measurements in HA solutions indicated translational and rotational diffusivities of the nanoparticles were higher than SE predictions based on the low shear viscosity measured in a rheometer. The ratio of the translational and rotational diffusivities was found to be proportional to the hydrodynamic diameter of the nanoparticles and independent of the concentration of HA in solution. Nanoscale viscosities determined from the measured diffusivities and SE relation using the measured hydrodynamic diameters were similar between nanoparticles and techniques, and corresponded to the high shear viscosity and the concentration dependent equation of viscosity for all HA concentrations. In case of synovial fluid, the translational and rotational diffusivities of the 44 nm particles were found to be in the same order as predicted from the high shear rate viscosity of synovial fluid. The translational and rotational diffusion coefficient of 220 nm were found to be lower than that predicted from the SE relation using the high shear viscosity, but was still about 50 times higher than expected based on the low shear rate viscosity of the synovial fluid. We believe these observations can be extended to the diffusion of nanoparticles in solutions of higher molecular weight and moderately flexible polymers which can have important implications to understanding the transport of nanoparticles in biological fluids.