Deliganding Carbonic Adsorbents for Simultaneous Removal of Protein-Bound Toxins, Bacterial Toxins and Inflammatory Cytokines

Abstract

In this work structural and sorption properties of granulated carbonic sorbents obtained by deep pyrolysis of synthetic resins, are described. It has been shown that these sorbents possess high (up to 2.7 cm³  g^-1) pore volume, low (up to 0.06 g  cm⁻³) bulk density, well developed supermicro- and mesoporosity and significantly fractal structure in the range from 75 to 900  Å. Upon contact with solutions of human serum albumin (HSA), they efficiently adsorb protein-bound ligands with association constants from 10³ to 10⁸ M⁻¹. These sorbents coded as HSGD (from HemoSorbent Granulated Deliganding) demonstrate adsorption capacity for unconjugated bilirubin, fatty and bile acids, phenols, CMPF, hippuric acid and indoxyl sulfate, which is tenfold higher than that for conventional granulated synthetic carbon hemosorbents. At the same time capacity of HSGD for freely soluble low molecular weight compounds, such as creatinine and methylene blue increases insignificantly. Simultaneously HSGD demonstrates high adsorption capacity for inflammatory cytokines TNF-α, IL-1, IL-6 that could be further enhanced by coating of the carbonic surface with native DNA or dextrane sulfate. Hemocompatibility of HSGD may be significantly increased by adding citrate to blood or by coating its surface with serum albumin. Finally, HSGD capacity coated with HSA for bacterial lipopolysaccharide (LPS) is by 15–20% higher than that of uncoated one. The use of certain molecular or pH-conformers of HSA for HSGD coating creates a diffusion “transparent” layer that practically does not affect the adsorption capacity of the carbonic matrix towards protein-bound ligands.

It has been demonstrated that the deep pyrolysis technology used to produce HSGD can be applied to other carbonic sorbents made from granular synthetic, natural and fibrous raw materials.