A System Establishing Compatibility Profiles for Artificial Oxygen Carriers and Other Substances

Abstract

Worldwide, great efforts are being made to develop a clinically useful artificial oxygen carrier. Toxicological and immunological compatibility is generally tested using animal experiments but inflammatory parameters in particular show large species-specific differences. Therefore, we developed an in vitro system using human components to establish a compatibility profile of unknown compounds. The test system comprises induction of hemolysis, activation of complement (C3a), induction/suppression of cytokine production, influence on cell proliferation, direct toxicity on peripheral leukocytes, and phagocytosis of the material under test and of microbes. The test system will be described, along with results of various perfluorocarbon emulsions. When testing lecithin-based perfluorodecalin (PFD) emulsions, and comparing them to Pluronic-based PFD emulsions, we could show that Pluronic-based emulsions were virtually untoxic to peripheral human leukocytes. They neither inhibited cell proliferation nor caused any hemolysis, but caused mild to moderate inhibition of endotoxin-induced cytokine production. At the same time, lecithin-based PFD emulsion caused substantial cytotoxicity in phagocytic cells like monocytes (60-100% after 24 h incubation) and granulocytes (10-20% after 24 h incubation). They also suppressed endotoxin-induced cytokine production in monocytes to more than 98% and inhibited cell proliferation of an endothelial (ECV 304) and a monocytic cell line (MonoMac6) to more than 95%.

<p>Impact of different emulsifiers on biocompatibility and inflammatory potential of Perfluorohexyloctane (F6H8) emulsions for new intravenous drug delivery systems</p>

“…Dinkelmann et al compared emulsions of the PFC Perfluorodecalin (PFD) emulsified with either Pluronic or lecithin 30. However, this study revealed contrasting findings.…”

Artifical Blood

“…Lecithin-based PFD emulsion caused substantial cytotoxicity in phagocytic cells like monocytes (60-100% after 24 hour incubation) and granulocytes (10-20% after 24 hour incubation). They also suppressed endotoxin-induced cytokine production in monocytes to more than 98% and inhibited cell proliferation of an endothelial (ECV 304) and a monocytic cell line (MonoMac6) to more than 95% [18]. However, an in-vivo trial of pluronic F-68 -based PFD led to adverse effects like intolerance of initial test dose, transient leucopenia, hypotension, chest pain, and a syndrome consisting of fever, leucocytosis and infiltrates on chest roentgenogram.…”

Artificial Oxygen Carriers - A Critical Analysis of Current Developments

“…Wichtig sind auch mögliche Nebenwirkungen des Emulgators. In eigenen Studien [9] wurde der Einfluss verschiedener PFD-Emulsionen auf humane Zellen untersucht: Dabei fanden wir für PFD/Lezithin-Emulsionen eine Zellproliferationshemmung bei monozytären und endothelialen Zellen (siehe auch Abb. 2), außerdem eine toxische Wirkung auf periphere Phagozyten, insbesondere Monozyten und eine Unterdrückung der Lipopolysaccharid (LPS) induzierten Ausschüttung von Interleukin 1b und Interleukin 6.…”