title: Albumin-derived perfluorocarbon-based artificial oxygen carriers: A physico-chemical characterization and first in vivo evaluation of biocompatibility.
abstract: Until today, artificial oxygen carriers have not been reached satisfactory quality for routine clinical treatments. To bridge this gap, we designed albumin-derived perfluorocarbon-based nanoparticles as novel artificial oxygen carriers and evaluated their physico-chemical and pharmacological performance. Our albumin-derived perfluorocarbon-based nanoparticles (capsules), composed of an albumin shell and a perfluorodecalin core, were synthesized using ultrasonics. Their subsequent analysis by physico-chemical methods such as scanning electron-, laser scanning- and dark field microscopy as well as dynamic light scattering revealed spherically-shaped, nano-sized particles, that were colloidally stable when dispersed in 5% human serum albumin solution. Furthermore, they provided a remarkable maximum oxygen capacity, determined with a respirometer, reflecting a higher oxygen transport capacity than the competitor Perftoran®. Intravenous administration to healthy rats was well tolerated. Undesirable effects on either mean arterial blood pressure, hepatic microcirculation (determined by in vivo microscopy) or any deposit of capsules in organs, except the spleen, were not observed. Some minor, dose-dependent effects on tissue damage (release of cellular enzymes, alterations of spleen's micro-architecture) were detected. As our promising albumin-derived perfluorocarbon-based nanoparticles fulfilled decisive physico-chemical demands of an artificial oxygen carrier while lacking severe side-effects after in vivo administration they should be advanced to functionally focused in vivo testing conditions.
authors.affiliation: University of Duisburg-Essen, Institute for Physiological Chemistry, University Hospital Essen, Hufelandstr. 55, 45122 Essen, Germany. Electronic address: anna.wrobeln@stud.uni-due.de.
authors.forename: Anna
authors.initials: A
authors.lastname: Wrobeln
authors.affiliation: University of Duisburg-Essen, Institute for Physiological Chemistry, University Hospital Essen, Hufelandstr. 55, 45122 Essen, Germany. Electronic address: julialaudien@gmx.de.
authors.forename: Julia
authors.initials: J
authors.lastname: Laudien
authors.affiliation: University of Duisburg-Essen, Institute for Physical Chemistry, CeNIDE, Universitaetsstr. 5, 45141 Essen, Germany. Electronic address: chrisgh@gmx.de.
authors.forename: Christoph
authors.initials: C
authors.lastname: Groß-Heitfeld
authors.affiliation: University of Duisburg-Essen, Institute for Physical Chemistry, CeNIDE, Universitaetsstr. 5, 45141 Essen, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Linders
authors.affiliation: University of Duisburg-Essen, Institute for Physical Chemistry, CeNIDE, Universitaetsstr. 5, 45141 Essen, Germany. Electronic address: christian.mayer@uni-due.de.
authors.forename: Christian
authors.initials: C
authors.lastname: Mayer
authors.affiliation: Department of Nephrology, University Hospital Essen, Hufelandstr. 55, 45122 Essen, Germany. Electronic address: benjamin.wilde@uk-essen.de.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Wilde
authors.affiliation: University of Duisburg-Essen, Institute for Physiological Chemistry, University Hospital Essen, Hufelandstr. 55, 45122 Essen, Germany. Electronic address: tanja.knoll@gmx.de.
authors.forename: Tanja
authors.initials: T
authors.lastname: Knoll
authors.affiliation: University of Duisburg-Essen, Institute of Inorganic Chemistry, CeNIDE, Universitaetsstr. 5, 45141 Essen, Germany. Electronic address: dominik.naglav@uni-due.de.
authors.forename: Dominik
authors.initials: D
authors.lastname: Naglav
authors.affiliation: University of Duisburg-Essen, Institute for Physiological Chemistry, University Hospital Essen, Hufelandstr. 55, 45122 Essen, Germany. Electronic address: michael.kirsch@uni-duisburg-essen.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Kirsch
authors.affiliation: University of Duisburg-Essen, Institute for Physiological Chemistry, University Hospital Essen, Hufelandstr. 55, 45122 Essen, Germany. Electronic address: katja.ferenz@uk-essen.de.
authors.forename: Katja B
authors.initials: KB
authors.lastname: Ferenz
mesh_terms: D000818:Animals; D062186:Arterial Pressure / Q000187:drug effects; D001672:Biocompatible Materials / Q000737:chemistry*; D002214:Capsules / Q000737:chemistry / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry*; D005466:Fluorocarbons / Q000737:chemistry*; D006801:Humans; D008297:Male; D053758:Nanoparticles / Q000737:chemistry; D010100:Oxygen / Q000737:chemistry* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D000075462:Serum Albumin, Human / Q000737:chemistry*; D012996:Solutions / Q000737:chemistry / Q000494:pharmacology
chemical_list: D001672:Biocompatible Materials; D002214:Capsules; D004337:Drug Carriers; D005466:Fluorocarbons; D012996:Solutions; C008805:perfluorodecalin; D010100:Oxygen; D000075462:Serum Albumin, Human
keywords: Albumin; Artificial oxygen carrier; Blood substitutes; Intravenous administration; Nanocapsules; Nanoparticles; Perfluorocarbon; Perfluorodecalin