(148d) Towards Understanding Nanoparticle Diffusion in Synovial Fluid Analogues

The
use of nanoparticles in complex biological environments has motivated study of their
dynamics in concentrated mixtures of macromolecules. Synovial fluid, a lubricant found in joints, is one such complex fluid,
with macromolecules like hyaluronic acid and lubricin as major constituents
that define its structure and function. Fundamental knowledge of how
nanoparticles diffuse in synovial fluid would help engineer better drug
delivery agents and also improve basic understanding of the structure of
synovial fluid. Here, we study the translation and rotation of magnetic
nanoparticles in synovial fluid analogues – concentrated suspensions of
hyaluronic acid.

Hyarulonic
acid (HA) solutions at concentrations where the HA molecules are well separated
(i.e., the dilute regime) and where they overlap (i.e., the semi-dilute regime)
were prepared as a first approach to mimic the composition of synovial fluid. Cobalt
ferrite particles of two hydrodynamic sizes (40 nm and 240 nm) with an outer
coating of polyethylene glycol were suspended in these HA solutions to study the
effect of particle size on hydrodynamic drag exerted by the complex fluid
matrix. The dynamic response of the particles to an applied alternating
magnetic field was analyzed to obtain their rotational diffusion coefficients
and, through the Stokes-Einstein relation, the apparent viscosity of the fluid.
We found that the average viscosities obtained from nanoscale measurements were
similar to that of water and did not correspond to the viscosity of the bulk
fluid as measured using a rheometer, for HA solutions in both the dilute and
semi-dilute regimes.  Control measurements of rotation of the particles in
glycerol solutions indicated that the viscosity determined by rotation of the
particles in simple fluids was similar to the bulk viscosity.

To
complement these measurements, semi-quantitative estimates of the relative
translational hydrodynamic drag on the nanoparticles was obtained through
measurements of the rate of magnetic capture. Magnetic nanoparticles were
subjected to an external magnetic field gradient and their translation was
monitored by the amount of particles recovered as a function of time.  The rate
of translation of particles in solutions in the semi-dilute regime was found to
be slower than for particles in solutions in the dilute regime, indicating
greater viscous drag experienced by the particles in the more concentrated HA
solutions. However, comparison to rates of capture in control glycerol
solutions with similar viscosity suggests that the translational hydrodynamic drag
experienced by the nanoparticles in the HA solutions is lower than expected
based on their macroscopic viscosity.

These
studies suggest that rotational motion of nanoparticles below 240 nm in
diameter is unimpeded by the HA network in these synovial fluid analogues,
whereas translation of the particles does appear to be impeded by the HA
network, albeit the effect is much less pronounced than expected based on
macroscopic rheological measurements. These observations provide insight into
the dynamics of nanoparticles in complex biological fluids and can serve to
develop novel nanoparticle-based drug delivery and diagnostic technologies
applicable in joint diseases.