Membrane adsorbers for selective endotoxin removal from protein solutions

Using polymer-coated microfiltration membranes, immobilisation of polymyxin B, deoxycholate, poly-L-lysine and poly(ethyleneimine) leads to membrane adsorbers with high selectivity for endotoxins and low mass transport restrictions. Clearance factors up to 100 000 for protein-free Escherichia coli filtrates and up to 10 000 for protein solutions are possible. Endotoxin levels can be reduced below the threshold levels required for parenteralia at residence times of only 6 s. Polycationic ligands are most effective in removing endotoxins from net-positively charged proteins, such as lysozyme, ribonuclease and human IgG. The same is true for net-negatively charged proteins at concentration up to 1 mg ml(-1) and at a pH close to the proteins' isoelectric points, as was shown for bovine and human serum albumin and a murine monoclonal antibody. At higher protein concentrations the ligand based on deoxycholate was most effective. This ligand was also most suitable for clearing endotoxins from blood serum and plasma. As the protein binding capacity of these membrane adsorbers is only 6-15 mg ml(-1) membrane volume, almost 100% protein recovery can be assured. (C) 2000 Elsevier Science Ltd. All rights reserved.