No abstract

Hyperbilirubinemia is one of the main causes of death in patients with severe hepatic problems, which justifies the research for bilirubin removal solutions. In this study, St-MMA particles with PEGMA and/or GMA brushes were synthesized. First, the recipe for St-MMA was optimized and then adapted for PEGMA and GMA incorporation. Different solvents were then assayed to improve the BSA immobilization capacity of the particles. Ethyl lactate proved to be the best solvent, reaching a BSA immobilization capacity improvement of up to 60% for St-MMA-GMA-PEGMA particles. These particles also presented the best results for BR removal from PBS. No significant differences in the final capacity for BR removal from PBS media were observed when BSA was attached to the particles; however, the kinetics were greatly improved, requiring half the time. Finally, St-MMA-GMA-PEGMA particles that were wetted in EL with BSA reduced the bilirubin concentration in plasma from levels that threaten the survival of critical patients to levels close to those of healthy individuals in less than 30 min. On the contrary, particles without BSA were unable to remove bilirubin from plasma. Thus, the attachment of albumin to the particles plays a key role in selectively reducing bilirubin levels.

The scale-up and the economic feasibility of the synthesis of St-MMA-GMA-PEGMA particles biofunctionalized with HSA were studied. First, the geometrical similarity of laboratory and pilot plant reactors was checked to develop the scale up of the process according to a criterion of partial similarity. The selected criterion was constant Re number. Then, a reaction in the pilot plant scale was carried out, confirming the suitability of the scale-up criterion, since particles with similar characteristics (same particle size with a deviation of just 6%) and functional groups were obtained. Finally, the design of an industrial plant able to produce 581 Tm/year of HSA functionalized St-MMA-GMA-PEGMA particles was addressed. The economic feasibility of this plant was confirmed by a value of internal rate of return (IRR) of 14.8% and a net present value (NPV) of 5452 M€, with a payback time between six and seven years, for the price of a cartridge 25% lower than that from the current treatments for bilirubin removal from patients with liver failure.

This work describes the development of styrene-divinylbenzene (St-DVB) particles with polyethylene glycol methacrylate (PEGMA) and/or glycidyl methacrylate (GMA) brushes for the removal of bilirubin from blood in haemodialyzed patients. Bovine serum albumin (BSA) was immobilized onto the particles using ethyl lactate as a biocompatible solvent, which allowed the immobilization of up to 2 mg BSA/g of particles. The presence of albumin on the particles increased their capacity for bilirubin removal from phosphate-buffered saline (PBS) by 43% compared to particles without albumin. The particles were tested in plasma, finding that St-DVB-GMA-PEGMA particles that had been wetted in ethyl lactate with BSA reduced the concentration of bilirubin in plasma by 53% in less than 30 min. This effect was not observed in particles without BSA. Therefore, the presence of albumin on the particles enabled quick and selective removal of bilirubin from plasma. Overall, the study highlights the potential use of St-DVB particles with PEGMA and/or GMA brushes for bilirubin removal in haemodialyzed patients. The immobilization of albumin onto the particles using ethyl lactate increased their capacity for bilirubin removal and enabled quick and selective removal from plasma.