Dextran-encapsulated barium sulfate nanoparticles prepared for aqueous dispersion as an X-ray contrast agent

Barium sulfate (BaSO4) nanoparticles (<= 100 nm) are of interest to provide improved performance over microscale BaSO4 particles, which are currently used clinically as an X-ray contrast agent or radiopacifier, and to further enable passive or targeted delivery of BaSO4 contrast agents. The stability of BaSO4 nanoparticle dispersions in aqueous media is critical for these uses but has received little attention. Therefore, the objective of this study was to prepare and characterize a BaSO4 nanoparticle contrast agent with colloidal stability in aqueous media. Monodisperse BaSO4 nanoparticles, similar to 13 nm in diameter, were synthesized using water-in-oil nanoemulsions wherein the aqueous droplet size limited particle growth and the surfactant layer provided a barrier against aggregation. The as-synthesized nanoparticles were readily redispersed in organic solvents but agglomerated when redispersed in aqueous media due to exhibiting a low, nearly isoelectric zeta potential at neutral pH. Therefore, the as-synthesized BaSO4 nanoparticles were subsequently encapsulated by crosslinked dextran within the nanoemulsion droplets in order to provide both steric and electrostatic stabilization upon breaking the nanoemulsion Dextran encapsulation increased the particle diameter to *40 nm, but enabled BaSO4 nanoparticles to be readily redispersed in water and maintain colloidal stability for more than a month. The X-ray attenuation of dispersed dextran-encapsulated BaSO4 nanoparticles was not different from that measured for either a commercial microscale BaSO4 suspension or a solution of barium ions prepared in water at an equal mass concentration of barium, but was significantly greater than the attenuation exhibited by soft tissues. Thus, dextran-encapsulated BaSO4 nanoparticles appear to be suitable for passive or targeted delivery as an X-ray contrast agent.