Improved Albumin-Derived Per Fluorocarbon- Based Artificial Oxygen Carriers: In-vivo Evaluation of Biocompatibility

Abstract

Despite long lasting efforts, an artificial oxygen carrier displaying adequate gas solubility combined with a minimal risk of side effects is missing at present for clinical use, both in Europe and USA. To bypass this bottleneck, recently developed albumin-derived per fluorocarbonbased nanocapsules were further improved and tested in-vivo. Most importantly, this second nanocapsule generation reached a smaller size distribution that resulted in partially less side effects compared to the first capsule formulation. The intravenous administration to healthy rats was tolerated without any noticeable abnormalities. Systemic and blood parameters stayed within the physiological range. Minor side-effects could be observed in the release of intracellular enzymes specific for organ damage. The intravascular half -life of the second generation of albumin-derived per fluorocarbon-based nanocapsules was ameliorated with regard to the first generation. Thus, the further improved albuminderived per fluorocarbon-based nanocapsules should be tested in much more advanced and clinical relevant models

Albumin-derived perfluorocarbon-based artificial oxygen carriers can avoid hypoxic tissue damage in massive hemodilution

“…We successfully synthesized nanoscaled PFOCs with a perfluorodecalin (PFD) core surrounded by a biocompatible albumin shell (capsules) 13 . Previous studies successfully describe the in vivo biocompatibility in a rat-top-load model and the functionality in an ex vivo isolated rat heart model 11,14,15 . Herein, we used a rat model of massive hemodilution, where we exchanged about 95% of the blood volume with either capsules in a plasma-like solution (treatment) or the plasma-like solution without capsules (control) and posthumously surveyed hypoxia sensitive organs such as the small intestine and kidney.…”

Perfluorocarbons for the treatment of decompression illness: how to bridge the gap between theory and practice

“…Amphiphilic albumin as shell material encloses a core of PFD, thus avoiding the requirement of an additional emulsifier. In vitro tests have shown effective oxygen transport capacity of A-AOCs (Wrobeln et al 2017b), further supported by the proof of functionality in the Langendorff-heart-model (Wrobeln et al 2017c) and in vivo studies of the rat regarding toxicity and pharmacokinetics (Wrobeln et al 2017a). Intravenous application of A-AOCs was well tolerated in rats without change in systemic parameters and with stabile vascular perfusion.…”

“…Parameters of tissue injury showed no relevant deviations and the half-life of A-AOCs (158 min) was sufficient (Wrobeln et al 2017b). An in vivo proof-of-concept-study then demonstrated survival of rats after progressive exchange of 95% of blood with A-AOCs (Wrobeln et al 2017a).…”

Current perspectives of artificial oxygen carriers as red blood cell substitutes: a review of old to cutting-edge technologies using in vitro and in vivo assessments

“…It has been used in cell lines (in vitro) and animal models (in vivo) to evaluate the efficacy and safety of PFC (Table 7 ). A new development of A-AOC showed better biocompatibility and longer half-life circulation, thus resulting in good oxygen transportation in different animal models (Wrobeln et al 2017b ; Ferenz 2017 ). It was well-tolerated by intravenous administration and gave higher oxygen transport capacity in rats compared to Perftoran® (Wrobeln et al 2017a ).…”