Polymyxin-Coated Nanostructured Materials: An Option for Sepsis Treatment

Abstract

Polymyxin-Coated Nanostructured Materials: An Option for Sepsis Treatment Objective: Endotoxins (lipopolysaccharides, LPS) are among the main targets in extracorporeal therapies. LPS, which is the major component of the outer cell wall of Gram-negative bacteria, strongly induces inflammatory responses in humans at concentrations lower than 1 ng/kg body weight. Although the elimination of LPS is promising for the supportive therapy of sepsis and liver failure, endotoxin neutralization using endotoxin adsorbents is controversial. Earlier studies show that Polymyxin B (PMB) could be applied for endotoxin inactivation in blood. Aim of this study was to establish an adsorbent-based PMB release system which ensures a constant PMB level in plasma during extracorporeal therapies. Methods: A polystyrene-divinylbenzene based cytokine adsorbent (CG161c) with nanostructured pores was coated with a defined amount of PMB by hydrophobic interactions. The PMB release by the PMB coated adsorbent was studied in plasma and fractionated plasma. Results: In plasma or blood, an equilibration between the free and bound form of PMB leads to a constant PMB level in plasma. The PMB release was influenced by the adsorbent inner surface area and the protein concentration of the plasma. In fractionated plasma where the protein concentration is lower, the PMB release was much less than in whole plasma. Additionally we could show that the PMB coating doesn´t influence the cytokine removal of the CG161c adsorbent. Conclusion: Our in vitro model shows that the combination of cytokine removal and controlled PMB release by the same adsorbent could be an option for Gram-negative sepsis treatment.