4431 PREPARATION OF IMIDAZOLE QUATERNARY AMMONIUM SALT MICROSPHERES WITH HIGH BILIRUBIN ADSORPTION PERFORMANCE AND SELF-ANTICOAGULATION ABILITY

Abstract Background and Aims Bilirubin is a crucial toxin in liver metabolism. Increase of bilirubin is one of common manifestations in patients with abnormal liver function, and large accumulation of bilirubin in the blood can lead to more severe hepatic dysfunction and even death. Due to the poor therapy effect and the shortage of available donor organs, the artificial liver support system has been introduced to maintain the liver function and bridge patients to transplantation. Previous studies have found that imidazole quaternary ammonium salts have great potential to adsorb bilirubin. This work is to develop a novel bilirubin adsorption column by simple and general method, and evaluate the removal efficiency, anticoagulant property and biocompatibility of the bilirubin adsorption column. Method Multifunctional microspheres were fabricated by in situ co-polymerization of 1-vinylimidazole and divinylbenzene. Nuclear magnetic resonance (NMR), thermo-gravimetric analysis and X-ray photoelectron spectroscopy (XPS) etc. were performed to characterize the chemical compositions of the microspheres. Meanwhile, hemolysis test, blood routine test and clotting time test etc. were leveraged to evaluate the biocompatibility of the microspheres. Both static adsorption test and dynamic adsorption test were performed in vitro to evaluate adsorption performance. Results A variety of methods had proved successful synthesis of the adsorption performance. The hemolysis ratios of microspheres were less than 5%. Compared with BS330 microspheres and PES microspheres, the activated partial thromboplastin time (APTT) and thrombin time (TT) were longer in this work. Moreover, the microspheres showed a high adsorption clearance. In PBS solution of bilirubin, the adsorbent could decrease bilirubin from 200 mg/L to 45-55 mg/L. Conclusion The results suggested that the multifunctional microspheres can significantly reduce bilirubin concentration without obvious adverse interactions and could exhibit anticoagulation activity.