Efficacy of graphene oxide-loaded cationic antimicrobial peptide AWRK6 on the neutralization of endotoxin activity and in the treatment of sepsis

Abstract

Objective: This study is to assess the therapeutic effect of graphene oxide (GO) loaded with AWRK6 on endotoxininduced sepsis. Method: AWRK6/GO was prepared by GO loaded AWRK6, with the structure characterization of AWRK6/GO conducted by atomic force microscope (AFM) and ultraviolet spectrophotometer, the sustained release rate of AWRK6/GO detected by high performance liquid chromatography (HPLC), and the neutralization ability of AWRK6/GO to lipopolysaccharide (LPS) tested by in vitro experiments. The levels of IL-8 and TNF-α in mouse cells after drug intervention were detected by ELISA; a LPS mouse model was established to observe the effects of drug intervention on the survival cycle and survival rate of mice. Results: The sustained drug release rate of AWRK6/GO reached 85% within 24 hours observed under in vitro conditions, with an efficient neutralization effect to LPS (P < 0.01); Compared with the control group, the intervention of LPS succeeded in remarkably elevating the levels of IL-8 and TNF-α in the whole blood and macrophages of the mice (P < 0.01), whose survival cycle and survival rate consequently observed an obvious decline (P < 0.01); The intervention with AWRK6 or AWRK6/GO predominantly brought down the levels of IL-8 and TNF-α in the whole blood and macrophages of mice given LPS (P < 0.01), resulting in an elevation of the survival rate and survival time (P < 0.01). Conclusion: GO loaded with cationic antimicrobial peptide AWRK6 exerts a rosy neutralization effect on endotoxin activity, with no obvious side effects on mice observed, which is of certain application value in the treatment of sepsis.