Development of cationically modified cellulose adsorbents for the removal of endotoxins

The removal of endotoxins by extracorporeal adsorption processes seems the most promising therapeutic approach to Gram-negative sepsis and endotoxin shock. However, thus far adsorbents have failed to bind endotoxins efficiently or have shown adverse biocompatibility characteristics. To overcome these disadvantages, small particles of regenerated cellulose in the range of 1-8 microns in diameter were produced. Before use, the microspheres were cationically modified by substitution with polyethyleneimine (PEI) or diethylaminoethyl (DEAE) groups. A third kind of adsorbent was manufactured by (physically) coating the cellulose matrix with PEI. All three types of adsorbents exhibited a high adsorption capacity for endotoxins in human plasma, whereas activated charcoal and various anion exchange resins removed only small amounts of endotoxins under the same conditions. In addition, because the outer surface area is very large, adsorption takes place rapidly and diffusion becomes almost irrelevant. The adsorption process is primarily based on electrostatic interactions, which could be demonstrated by a significantly higher adsorption rate and binding capacity for lipid A-diphosphoryl, compared with lipid A-monophosphoryl. Use of these adsorbents in a newly developed plasma sorption system could be of great clinical interest because of the low production costs, the high adsorption efficiency, and the excellent biocompatibility data.