Artificial Oxygen Carriers—Past, Present, and Future—a Review of the Most Innovative and Clinically Relevant Concepts

Ferenz, Katja Bettina; Steinbicker, Andrea U.

doi:10.1124/jpet.118.254664

Cited by 52 publications

(77 citation statements)

References 111 publications

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“…Short time later, new PFC emulsions such as Oxycyte and Oxygent were developed using egg yolk lecithin as emulsifier and further block polymers (Proxanol 268), which allow for the formation of smaller droplets (50–100 nm) with a higher charge density [ 50 , 62 ]. Those emulsions showed a higher stability, were heat sterilizable and could be stored frozen without decaying when thawing [ 23 , 101 ]. Decay of these second-generation emulsions is the result of a second process: Ostwald ripening.…”

Section: Pfc-based Oxygen Carriers: Emulsions Formation and Storagementioning

confidence: 99%

Section: Pfc-based Oxygen Carriers: Peculiarities and Fields Of Applimentioning

confidence: 99%

“…Within the few last years, there has been an important shift of paradigm from large-volume “blood replacement” (several litres) to a small-volume use (mostly 250–500 ml) of artificial oxygen carriers as “oxygen therapeutics” [ 23 ]. The major field of application for PFOCs is clearly the short-term blood replacement in cases of blood loss and many reviews already cover this topic [ 23 , 36 , 41 ]. So far, PFOCs can be divided into four subclasses considering the main PFC used in the product: (I) PFD-based PFOCs such as Fluosol-DA, Perftoran and A-AOCs, (II) PFOB-based PFOCs such as Oxygent, (III) tertbutylperfluorocyclohexane-based PFOCs such as Oxycyte and (IV) DDFP-based PFOCs.…”

Section: Pfc-based Oxygen Carriers: Peculiarities and Fields Of Applimentioning

confidence: 99%

“…Oxycyte successfully completed phase II trials but was abandoned by the sponsor in 2014 due to lack of patient enrolment and economic reasons. Oxygent reached phase III trials, was transiently abandoned because of safety issues that later were disproved to be product-related and is currently under clinical investigation in China [ 23 ].…”

Section: Pfc-based Oxygen Carriers: Peculiarities and Fields Of Applimentioning

confidence: 99%

“…However, the interest in synthetic blood substitutes only increased gradually until the HI-virus-contaminated-donor-blood-crisis arose in the 1980s and vigorously accelerated the developmental research on artificial blood substitutes [ 8 ]. The use of perfluorocarbons bears attractive advantages over blood: Unlimited availability, no transmittance of diseases and no dependence on blood types [ 23 ]. This review intends to introduce the reader to these astonishing materials, which offer so many more chances of application beyond ordinary blood substitution.…”

Section: Introductionmentioning

confidence: 99%

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Perfluorocarbon-based oxygen carriers: from physics to physiology

Jägers

Wrobeln

Ferenz

2020

Pflugers Arch - Eur J Physiol

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130

108

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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.

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Section: Pfc-based Oxygen Carriers: Emulsions Formation and Storagementioning

confidence: 99%

Section: Pfc-based Oxygen Carriers: Peculiarities and Fields Of Applimentioning

confidence: 99%

Section: Pfc-based Oxygen Carriers: Peculiarities and Fields Of Applimentioning

confidence: 99%

Section: Pfc-based Oxygen Carriers: Peculiarities and Fields Of Applimentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Perfluorocarbon-based oxygen carriers: from physics to physiology

Jägers

Wrobeln

Ferenz

2020

Pflugers Arch - Eur J Physiol

Self Cite

130

108

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Biomimetic Liposomal Nanoplatinum for Targeted Cancer Chemophototherapy

et al. 2021

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Photodynamic therapy (PDT) of cancer is limited by tumor hypoxia. Platinum nanoparticles (nano-Pt) as a catalase-like nanoenzyme can enhance PDT through catalytic oxygen supply. However, the cytotoxic activity of nano-Pt is not comprehensively considered in the existing methods to exert their multifunctional antitumor effects. Here, nano-Pt are loaded into liposomes via reverse phase evaporation. The clinical photosensitizer verteporfin (VP) is loaded in the lipid bilayer to confer PDT activity. Murine macrophage cell membranes are hybridized into the liposomal membrane to confer biomimetic and targeting features. The resulting liposomal system, termed "nano-Pt/VP@MLipo," is investigated for chemophototherapy in vitro and in vivo in mouse tumor models. At the tumor site, oxygen produced by nano-Pt catalyzation improves the VP-mediated PDT, which in turn triggers the release of nano-Pt via membrane permeabilization. The ultrasmall 3-5 nm nano-Pt enables better penetration in tumors, which is also facilitated by the generated oxygen gas, for enhanced chemotherapy. Chemophototherapy with a single injection of nano-Pt/VP@MLipo and light irradiation inhibits the growth of aggressive 4T1 tumors and their lung metastasis, and prolongs animal survival without overt toxicity.

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Hemoglobin–albumin clusters as an artificial O₂ carrier: Physicochemical properties and resuscitation from hemorrhagic shock in rats

et al. 2022

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A bovine hemoglobin (HbBv) or human adult hemoglobin (HbA) wrapped covalently by human serum albumins (HSAs), hemoglobin–albumin clusters (HbBv–HSA3 and HbA–HSA3), are artificial O2 carriers used as a red blood cell substitute. This article describes the physicochemical properties of the HbBv–HSA3 and HbA–HSA3 solutions, and their abilities to restore the systemic condition after resuscitation from hemorrhagic shock in anesthetized rats. The HbBv–HSA3 and HbA–HSA3, which have high colloid osmotic activity, showed equivalent solution characteristics and O2 binding parameters. Shock was induced by 50% blood withdrawal. Rats exhibited hypotension and significant metabolic acidosis. After 15 min, the rats were administered shed autologous blood (SAB), HbBv–HSA3, HbA–HSA3, or Ringer's lactate (RL) solution. Survival rates, circulation parameters, hematological parameters, and blood gas parameters were monitored during the hemorrhagic shock and for 6 h after administration. All rats in the SAB, HbBv–HSA3, and HbA–HSA3 groups survived for 6 h. The HbBv–HSA3 and HbA–HSA3 groups restored mean arterial pressure after the resuscitation. No remarkable difference was observed in the time courses of blood gas parameters in any resuscitated group except for the RL group. Serum biochemical tests showed increases in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in the HbBv–HSA3 and HbA–HSA3 groups compared to the SAB group. Therefore, we observed other rats awakened after resuscitation with HbA–HSA3 for 7 days. The blood cell count, AST, and ALT recovered to the baseline values by 7 days. All the results implied that HbBv–HSA3 and HbA–HSA3 clusters provide restoration from hemorrhagic shock as an alternative material for SAB transfusion.

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Artificial Oxygen Carriers—Past, Present, and Future—a Review of the Most Innovative and Clinically Relevant Concepts

Cited by 52 publications

References 111 publications

Perfluorocarbon-based oxygen carriers: from physics to physiology

Perfluorocarbon-based oxygen carriers: from physics to physiology

Biomimetic Liposomal Nanoplatinum for Targeted Cancer Chemophototherapy

Hemoglobin–albumin clusters as an artificial O₂ carrier: Physicochemical properties and resuscitation from hemorrhagic shock in rats

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Artificial Oxygen Carriers—Past, Present, and Future—a Review of the Most Innovative and Clinically Relevant Concepts

Cited by 52 publications

References 111 publications

Perfluorocarbon-based oxygen carriers: from physics to physiology

Perfluorocarbon-based oxygen carriers: from physics to physiology

Biomimetic Liposomal Nanoplatinum for Targeted Cancer Chemophototherapy

Hemoglobin–albumin clusters as an artificial O2 carrier: Physicochemical properties and resuscitation from hemorrhagic shock in rats

Contact Info

Product

Resources

About

Hemoglobin–albumin clusters as an artificial O₂ carrier: Physicochemical properties and resuscitation from hemorrhagic shock in rats