A highly biocompatible polyethyleneimine/sulfonated polysulfone hemoperfusion microsphere with tailored surface charge for rapid and efficient removal of major protein-bound uremic toxins from simulated human plasma

Conventional hemodialysis and hemodiafiltration prove less effective at removing protein-bound uremic toxins (PBUTs) from the bloodstream of end-stage renal disease patients, primarily because PBUTs cannot pass through the small pores in the polymeric membranes. Hemoperfusion is an extracorporeal blood purification technique that employs an adsorption mechanism to remove multiple uremic toxins from such patients. Yet, the efficacy of hemoperfusion is constrained by some limitations of contemporary adsorbents, such as suboptimal capacity to adsorb PBUTs and poor hemocompatibility, presenting significant barriers for their clinical application. To address these challenges, we engineered a tailored hemoperfusion adsorbent by compounding sulfonated polysulfone (SPSf) and polyethyleneimine (PEI) into polyethersulfone (PES) microspheres to effectively capture and remove PBUTs through electrostatic interactions. Specifically, we introduced sulfuric acid into the coagulation bath to increase the adsorption amount of the developed adsorbent (H-PES/SPSf@PEI microspheres), to neutralize strong positive charge of PEI and to improve hemocompatibility. The tailored H-PES/SPSf@PEI microspheres neither damage blood cells nor activate the complement pathway when they contact with human blood. Moreover, H-PES/SPSf@PEI microspheres have a high adsorption amount toward major PBUTs, including hippuric acid (HA, 34.24 mg/g), 3-indoleacetic acid (IAA, 49.19 mg/g), p-cresol sulfate (PCS, 40.31 mg/g) and indoxyl sulfate (IS, 128.67 mg/g) by fitting adsorption isotherms. In a simulated hemoperfusion setting, the removal ratio of IS, IAA, PCS and HA by H-PES/SPSf@PEI microspheres reaches nearly 75.33%, 41.73%, 44.36% and 21.11%, respectively, with 47.89% of IS, 40.64% of IAA, 44.42% of PCS and 37.35% of HA being removed from BSA solution. In conclusion, H-PES/SPSf@PEI microspheres hold a potential to eliminate PBUTs from patients with end-stage renal disease.