Hemocompatible polyethylenimine-grafted poly (glycidyl methacrylate) based microspheres for effective endotoxin removal

Abstract

Endotoxin (also known as lipopolysaccharide, LPS), the major component in the outer cell wall of Gram-negative bacteria, is considered to be a main cause of sepsis. To reduce the mortality of sepsis, adsorbents with positively charged surfaces like polyethylenimine (PEI) are commonly employed to adsorb endotoxins; however, there are hidden dangers in binding stability and hemocompatibility of PEI-grafted materials. Herein, poly (glycidyl methacrylate) microspheres prepared by electro-spraying are chosen as the substrate, the surface epoxy groups are utilized to chemically immobilize PEI molecules. Then, heparin coatings are introduced through electrostatic interaction to obtain composite microspheres as hemoperfusion adsorbent. As a result, the hemocompatibility of the microspheres is significantly improved after the introduction of the heparin coatings. Compared to the microspheres only grafting PEI, the hemolysis ratio has a huge decrease from 4.6% to 1.0%. The adsorption process of the composite microspheres is more consistent with Sips isotherm model with a theoretical maximum endotoxin adsorption capacity of 2659.1 EU/g in normal saline solution. And the microspheres exhibit high endotoxin clearance ratio of 81.3% in static plasma (C0 = 12.6 EU/mL, exceeding critical illness level). In vitro dynamic adsorption experiments also indicate that the microspheres remove 86.6% of endotoxin in septic plasma (C0 = 7.2 EU/mL, exceeding critical illness level) within 1 h. We hope that the composite microspheres could have good application potential as an efficiency endotoxin adsorbent in sepsis treatment.