Synthesis and Characterization of BaSO4-CaCO3-Alginate Nanocomposite Materials as Contrast Agents for Fine Vascular Imaging.

Abstract

Microcomputed tomography is an important technique for distinguishing the vascular network from tissues with similar X-ray attenuation. Here, we describe a composite of barium sulfate (BaSO4) nanoparticles, calcium carbonate (CaCO3) nanoparticles, and alginate that provides improved performance over microscale BaSO4 particles, which are currently used clinically as X-ray contrast agents. BaSO4 and CaCO3 nanoparticles were synthesized using a polyol method with tetraethylene glycol as solvent and capping agent. The nanoparticles show good colloidal stability in aqueous solutions. A deliverable nanocomposite gel contrast agent was produced by encapsulation of the BaSO4 and CaCO3 nanoparticles in an alginate gel matrix. The gelation time was controlled by addition of d-(+)-gluconic acid δ-lactone, which controls the rate of dissolution of the CaCO3 nanoparticles that produce Ca2+ which cross-links the gel. Rapid cross-linking of the gel by Ba2+ was minimized by producing BaSO4 nanoparticles with an excess of surface sulfate. The resulting BaSO4-CaCO3 nanoparticle alginate gel mechanical properties were characterized, including the gel storage modulus, peak stress and elastic modulus, and radiodensity. The resulting nanocomposite has good viscosity control and good final gel stiffness. The nanocomposite has gelation times between 30 and 35 min, adequate for full body perfusion. This is the first nanoscale composite of a radiopaque metal salt to be developed in combination with an alginate hydrogel and designed for medical perfusion and vascular imaging applications.