Fabrication of gelatin Bi2S3 capsules as a highly sensitive X-ray contrast agent for gastrointestinal motility assessment in vivo

Abstract

Tiny BaSO₄ rod-based X-ray imaging is the most frequently-used method for clinical diagnosis of gastrointestinal motility disorders. The BaSO₄ rods usually have a small size to pass through the gastrointestinal tract smoothly, but suffer from unavoidably low sensitivity. Herein, we developed Bi₂S₃ capsules as a high-performance X-ray contrast agent for gastrointestinal motility assessment for the first time. The Bi₂S₃ capsules were synthesized by the encapsulation of commercial Bi₂S₃ powder into commercial gelatin capsules and subsequent coating of ultraviolet-curable resin. The prepared Bi₂S₃ capsules showed excellent biocompatibility in vitro and in vivo and superior X-ray attenuation ability due to the large atomic number and high K-edge value of Bi. The developed Bi₂S₃ capsules can serve as a small but highly sensitive X-ray contrast agent to quantitatively assess gastrointestinal motility in a vincristine-induced gastrointestinal motility disorder model in vivo by X-ray, CT and spectral CT imaging successfully, solving the intrinsic drawbacks of clinically used BaSO₄.

Scheme 1. Schematic illustration of synthesis of Bi₂S₃ capsules as a X-ray contrast agent for gastrointestinal tract visualization in vivo.

Fig. 1. Characterization of Bi₂S₃ powder and capsules. (A) The photo of commercial Bi₂S₃ powder. (B) The photo of dispersed Bi₂S₃ power in millimeter scale. (C) X-ray diffraction pattern of Bi₂S₃ powder. (D) The photo of empty gelatin capsule (upper panel) and Bi₂S₃ capsules (lower panel).

Fig. 2. HU curves and CT images of Bi₂S₃, BaSO₄ and iohexol suspensions with different concentrations of radiopaque elements (0.0125, 0.025, 0.05, 0.1, and 0.2 M Bi, Ba or I) at (A) 80 kV, (B) 100 kV, (C) 120 kV, (D) 140 kV.

Fig. 3. HU curves and spectral CT images of Bi₂S₃, BaSO₄ and iohexol suspensions at different concentrations of radiopaque elements (0.0125, 0.025, 0.05, 0.1, and 0.2 M Bi, Ba or I) at (A) 40 keV, (B) 80 keV, (C) 120 keV. (D) Spectral CT HU curves and images of Bi₂S₃, BaSO₄ and iohexol (0.1 M Bi, Ba or I) at different monochromatic energies.

Fig. 4. Spectral CT images and HU values of full of Bi₂S₃, BaSO₄ and iohexol capsules.

Fig. 5. X-ray images of rats after various treatments at different time points (0 min, 5 min, 2 h, 4 h, 8 h, 10 h) in vivo. (A) Control group (C group), (B) vincristine-treated group (V group), (C) vincristine & AM251 treated group (V&A group).

Fig. 6. The total scores (A) and lead capsule scores (B) of X-ray imaging of rats after various treatments at different time points. These data were shown as means ± SD, n = 8, evaluated by one-way analysis of variance, *p < 0.05, **p < 0.01.

Fig. 7. Three-dimensional reconstructed images of rats under different monochromatic energies after various treatments at different time points (0 min, 5 min, 2 h, 4 h, 8 h, 10 h) in vivo. (A) Control group (C group), (B) vincristine-treated group (V group), (C) vincristine & AM251 treated group (V&A group).