Perfluorocarbon-based oxygen carriers: from physics to physiology
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INVITED REVIEW
Perfluorocarbon-based oxygen carriers: from physics to physiology Johannes Jägers 1 & Anna Wrobeln 1 & Katja B. Ferenz 1,2 Received: 21 June 2020 / Revised: 12 October 2020 / Accepted: 16 October 2020 # The Author(s) 2020
Abstract Developing biocompatible, synthetic oxygen carriers is a consistently challenging task that researchers have been pursuing for decades. Perfluorocarbons (PFC) are fascinating compounds with a huge capacity to dissolve gases, where the respiratory gases are of special interest for current investigations. Although largely chemically and biologically inert, pure PFCs are not suitable for injection into the vascular system. Extensive research created stable PFC nano-emulsions that avoid (i) fast clearance from the blood and (ii) long organ retention time, which leads to undesired transient side effects. PFC-based oxygen carriers (PFOCs) show a variety of application fields, which are worthwhile to investigate. To understand the difficulties that challenge researchers in creating formulations for clinical applications, this review provides the physical background of PFCs’ properties and then illuminates the reasons for instabilities of PFC emulsions. By linking the unique properties of PFCs and PFOCs to physiology, it elaborates on the response, processing and dysregulation, which the body experiences through intravascular PFOCs. Thereby the reader will receive a scientific and easily comprehensible overview why PFOCs are precious tools for so many diverse application areas from cancer therapeutics to blood substitutes up to organ preservation and diving disease. Keywords Artificial oxygen carriers . Perfluorocarbon emulsion . Perfluorocarbon-based artificial oxygen carrier . CYP450 uncoupling . Reticuloendothelial system uptake . Perfluorocarbon excretion
Introduction Humankind has pursued the idea of rejuvenation and blood substitution since ancient times. In 8 AD, Ovid versified his thoughts on the magician Medea who—with a complex mixture of plants, stones and sand she had collected for 9 nights and 9 days—successfully regenerated the blood of the doter Aeson who rejuvenated into a 40-year-old man [45]. The first effective inter-human blood transfusion was performed on September 1st 1818, by James Blundell. But as human blood has always been a very precious and finite good, Amberson and Rhode were among the first researchers mixing isolated red blood cells (RBCs) from cattle, cats, dogs or humans with Ringer’s solution to simulate human blood in the 1930s [1]. They focused on the main ability of blood: Oxygen (O2)
* Katja B. Ferenz [email protected] 1
University of Duisburg-Essen, Institute of Physiology, University Hospital Essen, Hufelandstraße 55, 45122 Essen, Germany
2
CeNIDE (Center for Nanointegration Duisburg-Essen) University of Duisburg-Essen, Carl-Benz-Strasse 199, 47057 Duisburg, Germany
transport via RBCs. It took until the 1960s for the first artificial oxygen carriers made of engineered haemoglobin or other synthetic compounds to replace RBCs in b
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