Removal of endotoxin from protein solution using poly(#epsilon#-lysine)-immobilized cellulose beads

摘要

Endotoxin (Lipopolysaccharide [LPS], a constituent of cell walls of gram-negative bacteria, is a potential contaminant of physiological fluids and aqueous solutions. Even if present in only nanogram quantities, endotoxin has to be removed from solutions used for intravenous injections of drugs because its potent biological activities can cause pyrogenic and shock reactions in mammals? Recently, it has been suggested that the removal of endotoxin is extremely difficult when it is associated with theprotein to be purified. Various cationic polymer adsorbents, such as polymyxin-immobilized Sepharose (Pierce Chemical Co., Rockford, IL) and histamine-immobilized or histidine-immobilized Sepharose, have already been used for removing LPS from protein solutions. However, it has been reported that these adsorbents cannot selectively remove endotoxin from acidic protein solutions, such as bovine serum albumin (BSA), because of their high adsorbing activities for both endotoxin and BSA. In addition, polymyxin B and histamine, which have been used as ligands, are biologically active substances and thus are not suitable as ligands for removing endotoxin from an injection solution.