Blood Substitutes: Possibilities with Nanotechnology (original) (raw)
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Single Haemoglobin Nanocapsules as Test Materials for Artificial Blood
Periodica Polytechnica Chemical Engineering, 2014
Single protein nanocapsules (SPNs) means that each individual protein molecules are coated with a very thin polymer layer. The polymer chains which are porous enough to allow enzymatic functions are bound covalently to the protein molecule. According to our previous results the polymer layer can essentially stabilize different types of enzymes, e.g. its stability became to 50-70 times longer than that of the native ones. The heat stability (at 80 °C SPNs has activity after 24 hours) and the pH-stability (from pH = 1.5 to pH = 12.0) of the covered enzyme can essentially be improved comparing to the native enzymes. Our results show, that SPNs have a good features as drug carriers: acrylamide-bisacrylamide copolymer layer can carries bovine serum albumin molecules across the blood brain barrier in rat brain. We synthesized single haemoglobin nanocapsules with acrylamide-bisacrylamide copolymer on the surface of the molecules (PAAHgB) and their size, homogeneity, aggregation status, zeta potential were investigated compared with other nanomaterials.
International Journal of Molecular Sciences, 2023
The established blood donation and transfusion system has contributed a lot to human health and welfare, but for this system to function properly, it requires a sufficient number of healthy donors, which is not always possible. Pakistan was a country hit hardest by COVID-19 which additionally reduced the blood donation rates. In order to address such challenges, the present study focused on the development of RBC substitutes that can be transfused to all blood types. This paper reports the development and characterization of RBC substitutes by combining the strategies of conjugated and encapsulated hemoglobin where magnetite nanoparticles would act as the carrier of hemoglobin, and liposomes would separate internal and external environments. The interactions of hemoglobin variants with bare magnetite nanoparticles were studied through molecular docking studies. Moreover, nanoparticles were synthesized, and hemoglobin was purified from blood. These components were then used to make conjugates, and it was observed that only the hemoglobin HbA1 variant was making protein corona. These conjugates were then encapsulated in liposomes to make negatively charged RBC substitutes with a size range of 1–2 µm. Results suggest that these RBC substitutes work potentially in a similar way as natural RBCs work and can be used in the time of emergency.
Recombinant Hemoglobins as Artificial Oxygen Carriers
Artificial Cells, Blood Substitutes and Biotechnology, 2007
This paper describes the approaches we have taken to construct a) mutant hemoglobins with different oxygen affinities, and b) mutant hemoglobins and myoglobins that polymerize to high molecular weight aggregates in an effort to prevent extravasation and the associated vasoactivity. In vivo testing indicates that exchange transfusion of polymeric hemoglobins in mice does not result in vasoactivity and that polymeric hemoglobins are effective oxygen carriers to ischemic tissues irrespective of their oxygen affinity and cooperativity.
Biomacromolecules, 2014
The nonheme peroxidase, rubrerythrin, shows the ability to reduce hydrogen peroxide to water without involving strongly oxidizing and free-radical-creating powerful oxidants such as compounds I and II [formally Fe(IV)] formed in peroxidases and catalases. Rubrerythrin could, therefore, be a useful ingredient in protein-based artificial oxygen carriers. Here, we report that the oxygen-carrying proteins, hemoglobin (Hb) and hemerythrin (Hr), can each be copolymerized with rubrerythrin using glutaraldehyde yielding high molecular weight species. These copolymers show additional peroxidase activity compared to Hb-only and Hr-only polymers, respectively and also generate lower levels of free radicals in reactions that involve hydrogen peroxide. Tests on human umbilical vein endothelial cells (HUVEC) reveal slightly better performance of the Rbr copolymers compared to controls, as measured at 24 h, but not at later times.
The development of hemoglobin solutions as red cell substitutes: hemoglobin solutions
Transfusion science, 1995
Although the efficacy of hemoglobin-based oxygen carriers was established more than 60 years ago, all prior clinical trials have demonstrated significant toxicity characterized by renal dysfunction, gastrointestinal distress, and systemic vasoconstriction. The mechanisms of these toxicities now appear to be understood. Tetrameric forms of the hemoglobin molecule extravasate from the circulation and interact with endothelial derived relaxing factor, leading to unopposed vasoconstriction. Although numerous efforts are underway to chemically modify the native tetramer, it is likely that all tetrameric forms of the hemoglobin molecule will continue to extravasate. We have focused on developing a polymerized form of hemoglobin that is virtually free of unreacted tetramer. The development and characterization of this polymerized pyridoxylated hemoglobin solution (Poly SFH-P) is described. Clinical trials have been completed successfully in volunteers, and are now underway to assess the sa...
NANOTECHNOLOGYBLOODBRAINBARRIERANDNANOENCAPSULATION (4)
NANOTECHNOLOGYBLOODBRAINBARRIERANDNANOENCAPSULATION, 2024
Abstract The primary characteristic of flavonoids is their capacity to act as an antioxidant or radical scavenger, protecting cells from oxidative damage. The high reactivity of flavonoids' hydroxyl group renders free radicals inactive; instead, radicals change flavonoids into less reactive radicals, this chapter focused on important of curcumin and it encapsulated in calcium phosphate nanoparticles in an attempt to explore its antioxidant potential as a noble medication for neurological conditions. Thus, blood-brain barrier penetration may be improved by encapsulated nanoparticles, Conculusion: Novel approaches in nanobiotechnology, particularly tactics based on nano delivery, are now being studied to overcome the present limitations on curcumin bioavailability. Key words: curcumin, nanobiotechnology and bioavailabilitity
Journal of Pharmaceutical Investigation
Background Several circumstances such as accidents, surgery, traumatic hemorrhagic shock, and other causalities cause major blood loss. Allogenic blood transfusion can be resuscitative for such conditions; however, it has numerous ambivalent effects, including supply shortage, needs for more time, cost for blood grouping, the possibility of spreading an infection, and short shelf-life. Hypoxia or ischemia causes heart failure, neurological problems, and organ damage in many patients. To address this emergent medical need for resuscitation and to treat hypoxic conditions as well as to enhance oxygen transportation, researchers aspire to achieve a robust technology aimed to develop safe and feasible red blood cell substitutes for effective oxygen transport. Area covered This review article provides an overview of the formulation, storage, shelf-life, clinical application, side effects, and current perspectives of artificial oxygen carriers (AOCs) as red blood cell substitutes. Moreover, the pre-clinical (in vitro and in vivo) assessments for the evaluation of the efficacy and safety of oxygen transport through AOCs are key considerations in this study. With the most significant technologies, hemoglobin-and perfluorocarbon-based oxygen carriers as well as other modern technologies, such as synthetically produced porphyrin-based AOCs and oxygen-carrying micro/ nanobubbles, have also been elucidated. Expert opinion Both hemoglobin-and perfluorocarbon-based oxygen carriers are significant, despite having the latter acting as safeguards; they are cost-effective, facile formulations which penetrate small blood vessels and remove arterial blockages due to their nano-size. They also show better biocompatibility and longer half-life circulation than other similar technologies. Keywords Red blood cell substitutes • Artificial oxygen carriers • Old to cutting-edge technologies • In vitro and in vivo assessment Nijaya Mohanto and Young-Joon Park have contributed equally to this work as first authors.
Clinical Development of Human Polymerized Hemoglobin as a Blood Substitute
World Journal of Surgery, 1996
Although the efficacy of hemoglobin-based oxygen carriers was established more than 60 years ago, all prior clinical trials have demonstrated significant toxicity characterized by renal dysfunction, gastrointestinal distress, and systemic vasoconstriction. The mechanisms of these toxicities now appear to be understood. Tetrameric forms of the hemoglobin molecule extravasate from the circulation and interact with endothelium-derived relaxing factor, leading to unopposed vasoconstriction. Although numerous efforts are under way to chemically modify the native tetramer, it is likely that all tetrameric forms of the hemoglobin molecule will continue to extravasate. We have focused on developing a polymerized form of hemoglobin that is virtually free of unreacted tetramer. The development and characterization of this polymerized pyridoxylated hemoglobin solution (Poly SFH-P) is described. Clinical trials have been completed successfully in volunteers and are now under way to assess the safety and efficacy of Poly SFH-P as a clinically useful red blood cell substitute for treatment of acute blood loss in the setting of trauma and surgery.
Frontiers in Immunology, 2020
Intravenous injection of nanopharmaceuticals can induce severe hypersensitivity reactions (HSRs) resulting in anaphylactoid shock in a small percentage of patients, a phenomenon explicitly reproducible in pigs. However, there is a debate in the literature on whether the pig model of HSRs can be used as a safety test for the prediction of severe adverse reactions in humans. Given the importance of using appropriate animal models for toxicity/safety testing, the choice of the right species and model is a critical decision. In order to facilitate the decision process and to expand the relevant information regarding the pig or no pig dilemma, this review examines an ill-fated clinical development program conducted by Baxter Corporation in the United States 24 years ago, when HemeAssist, an αα (diaspirin) crosslinked hemoglobin-based O 2 carrier (HBOC) was tested in trauma patients. The study showed increased mortality in the treatment group relative to controls and had to be stopped. This disappointing result had far-reaching consequences and contributed to the setback in blood substitute research ever since. Importantly, the increased mortality of trauma patients was predicted in pig experiments conducted by US Army scientists, yet they were considered irrelevant to humans. Here we draw attention to that the underlying cause of hemoglobin-induced aggravation of hemorrhagic shock and severe HSRs have a common pathomechanism: cardiovascular distress due to vasoconstrictive effects of hemoglobin (Hb) and reactogenic nanomedicines, manifested, among others, in pulmonary hypertension. The main difference is that in the case of Hb this effect is due to NO-binding, while nanomedicines can trigger the release of proinflammatory mediators. Because of the higher sensitivity of cloven-hoof animals to this kind of cardiopulmonary