Haemocompatibility of nanoporous activated carbon adsorbents designed for blood detoxification

摘要

Nanostructured carbon materials offer great potential in the treatment of inflammation and infection. For example nanoporous, phenolic resin derived activated carbon adsorbents are well characterised as powerful adsorbents of difficult to remove high molecular weight and albumin bound toxins including bilirubin, indoxyl sulphate (IS) and p-cresyl sulphate (p-CS) and inflammatory cytokines such as interiukin-6 (IL6) and tumor necrosis factor alpha (TNFa). However, there are challenges in the use of activated carbons for blood perfusion applications including poor haemocompatibility, fine particle release and plasma protein adsorption. The following study describes haemocompatibility and efficacy testing for a range of adsorbent nanostructured carbons synthesised in bead and monolith form. Activated carbons were prepared by first curing the phenolic resin precursors in ethylene glycol at an elevated temperature of over 120 °C with agitation. The cured resin in bead form can be carbonised and activated to produce activated carbon beads or the resin can be extruded into a monolith format with parallel channels within, before carbonisation and activation. Adsorption efficacy of the resulting ACs was confirmed in vitro using toxin markers IL-6 (1ng/ml), TNFa (1 ng/ml), p-CS (250 μM) and IS (125 μm) from spiked human plasma. The results showed efficient removal of p-CS, IS, IL6 and significant removal of TNFa by both AC beads and monoliths. Using an ex vivo recirculating test system (Figure 1), 20 ml of freshly donated, anticoagulated healthy donor blood was perfused through AC monoliths (7mm diameter × 95mm length) or AC packed bead (2ml) columns at a flow rate of 5 ml/min. The haemocompatibility of the AC materials was evaluated by measuring blood biochemistry indicators, changes in blood protein concentration, electrolyte balance and the activation of platelets and the complement system. The results suggested minimum disruption in electrolyte and key blood protein parameters including albumin and fibrinogen concentration. Further investigation revealed that the use of AC materials in an ex vivo perfusion model did not trigger complement cascade activation, or platelet activation when compared to the control system running without the AC materials. The results indicate that the materials are haemocompatible and suitable for use as adsorbents for blood perfusion applications. Figure 1 Schematic illustration of the fresh healthy donor blood recirculation testing set up (a) and the image of the blood perfuse through AC monolith (b) and AC packed bead columns (c).