Synthesis and Characterization of BaSO(4)–CaCO(3)–Alginate Nanocomposite Materials as Contrast Agents for Fine Vascular Imaging

[Image: see text] 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 (BaSO(4)) nanoparticles, calcium carbonate (CaCO(3)) nanoparticles, and alginate that provides improved performance over microscale BaSO(4) particles, which are currently used clinically as X-ray contrast agents. BaSO(4) and CaCO(3) 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 BaSO(4) and CaCO(3) 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 CaCO(3) nanoparticles that produce Ca(2+) which cross-links the gel. Rapid cross-linking of the gel by Ba(2+) was minimized by producing BaSO(4) nanoparticles with an excess of surface sulfate. The resulting BaSO(4)–CaCO(3) 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.