MEMBRANE ADSORBERS FOR SELECTIVE REMOVAL OF BACTERIAL-ENDOTOXIN

Surface-modified flat-sheet microfiltration membranes were functionali sed with poly-L-lysine, polymyxin B, poly(ethyleneimine), L-histidine, histamine, alpha-amylase and DEAE as well as deoxycholate. Their suit ability to remove endotoxin from both buffers and protein solutions wa s examined using bovine serum albumin, murine IgG, and lysozyme as mod el proteins. In protein-free solutions reduction from 6000 EU/ml to <0 .1 EU/ml was achieved with all applied ligands; only alpha-amylase as well as L-histidine and histamine, when immobilized via the non-ionic spacer bisoxirane, exhibited low clearance factors at neutral pH. The adsorption of endotoxin is mainly ruled by electrostatic interaction f orces. Thus in multi-component systems, such as endotoxin-contaminated protein solutions, competing interactions take place: acidic proteins compete with endotoxin for binding sites at the membrane adsorbers, b asic proteins compete with the ligands for endotoxin and act as endoto xin carriers. With properly chosen conditions the membrane adsorbers p resented here show exceptional effectiveness also in the presence of p roteins. They are generally superior to functionalised Sepharose chrom atographic sorbents and allow fast processing. They may contribute to reduce the risks in the application of parenterals and diagnostics.