Chelating Effect Of The Novel Radionuclide Chelating Agent Chitosan-EDTA Nanoparticle In Vivo

Objective:To research and develop a new radionuclide chelating agent Chitosan-EDTA (CTS-EDTA) nanoparticles (CEC-Nano), investigate its promote exclusive effect on the polluted radioactive strontium radionuclide in mice, and provide experimental data for the development of a novel, highly efficient, broad-spectrum contaminative radionuclide chelating pharmaceutical.Method:The low molecular weight chitosan(CTS) with chelating ability and fine biocompatibility was connected with EDTA by N-acylation reaction. The CEC-Nano, which may be powerful chelating ability and special biological characteristics of nano-materials, was prepared by cross-linking CTS-EDTA with sodium tripolyphosphate(TPP).The radionuclide chelating effect of CEC-Nano in mice was investigated by survey and evaluating the radioactivity of radioactive strontium 89 in thighbone, collected urine and feces, collected residual ash of whole body, which was compared with non–nanomaterial CEC and EDTA-Na2. In addition, the residual strontium 89 in the mice was evaluated by small animal whole imaging.Results: The prepared CTS-EDTA-Nano nanoparticle (CEC-Nano) was a uniform spherical nanoparticle (PDI = 0.573), and the average particle diameter was 10.18 nm, determined by laser particle size analyzer and transmission electron microscopy.The einmal dose experiment had been carried out, and the chelating agents were injected one time by mouse caudal vein respectively. The radioactivity of strontium 89 accumulated in mouse thighbone was decreased significantly (p<0.05) after injection. Especially at the 30min and 2h after drug administration, the chelating effect of CEC-Nano and CEC was more effective than that of EDTA-Na2 significantly (p<0.05), and the CEC-Nano showed higher efficiency than non-nanomaterial CEC (p<0.05). However, at the 48h after administration, the chelating effect between CEC-Nano and CEC was no statistical difference (p>0.05). The repeated dose experiments had been carried out and the chelate agents were injected three times per day by mouse caudal vein respectively. The main excretion way of polluted radioactive strontium was the digestive and urinary systems. Within 48 hours, the chelating effect of CEC-Nano and CEC was stronger than that of the conventional chelator EDTA-Na2 by compared the radioactivity of strontium 89 in collected excrete urine and feces (p<0.05), and the CEC-Nano was better than the CEC (p<0.05). However, after 72 hours, there was no difference between CEC-Nano and CEC (p>0.05). The similar result had been confirmed by measuring the radioactivity of the collected residual ash of whole body. Within 48 hours, the chelating effect of CEC-Nano was better than that of CEC and EDTA-Na2 (p<0.05). After 72 hours, there was no difference between CEC-Nano and CEC (p>0.05). The residual strontium 89 in the mice was also calculated by drawn ROI on the whole mouse radioactive image. It was confirmed that the CEC-Nano had stronger chelating effect than the CEC and traditional chelating drugs EDTA-Na2 during 48 hours after injection (p<0.05). Even after 72 hours, the chelating effect of CEC-Nano was still better than that of CEC and EDTA-Na2 (p<0.05).Conclusion: A novel nanoparticle agent CEC-Nano for polluted radionuclide chelating had been developed. These results above mentioned had confirmed the advantages of the nano-formulation chelating agent. Not only may it be a powerful chelating agent of polluted radioactive strontium 89, but also a broad-spectrum radionuclide chelating agent potentially.