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2013 | OriginalPaper | Chapter

1. From Hemoglobin Based Oxygen Carrier to Oxygen Therapeutics, Blood Substitutes, Nanomedicine and Artificial Cells

Author : Thomas Ming Swi Chang

Published in: Hemoglobin-Based Oxygen Carriers as Red Cell Substitutes and Oxygen Therapeutics

Publisher: Springer Berlin Heidelberg

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Abstract

Hemoglobin (Hb), a tetrameric protein, is responsible for the transport of oxygen in red blood cells (Perutz 1980). Attempts to use hemolysate (Amberson 1937) and stroma-free Hb as Hb based oxygen carrier (Rabiner et al. 1967) resulted in nephrotoxicity and cardiovascular adverse effects (Savitsky et al. 1978). Thus, nanobiotechnological modification is needed before it can be used (Chang 1964)

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next chapter From the Atmosphere to the Mitochondrion: The Oxygen Cascade
Literature
Abuchowski A, Es TV, Palczuk NC Davis FF (1977) Alteration of immunological properties of bovine serum albumin by covalent attachment of polyethylene glycol. J Biol Chem 252: 2578–3581
Bangham AD et al (1965) Diffusion of univalent ions across the lamellae of swollen phospholipids. J Mol Biol 13:238–252
Alayash AI (2004) Oxygen therapeutics: can we tame Hb? Nat Rev Drug Discov 3:152–159CrossRef
Bian Y, Rong Z, Chang TMS (2011) Polyhemoglobin-superoxide dismutase-catalase-carbonic anhydrase: a novel biotechnology-based blood substitute that transports both oxygen and carbon dioxide and also acts as an antioxidant artificial cells. Blood Substitut Biotechnol 39:127–136CrossRef
Bian YZ, Wei G, Chang TMS (2013a) Lowering of elevated tissue PCO2 in a hemorrhagic shock rat model after reinfusion of a novel nanobiotechnological polyhemoglobin-superoxide dismutase-catalase-carbonic anhydrase that is an oxygen and carbon dioxide carrier with enhanced antioxidant properties. Artif Cells Nanomed Biotechnol 41:60–68CrossRef
Bian YZ, Yang L, Chang TMS (2013). Freeze dried polyhemoglobin-superoxide dismutase-catalase-carbonic anhydrase powder maintains long term stability at 37C, 20C, 4C and −70C (to be submitted)
Biro GP, Ou C, Ryan-MacFarlane C, Anderson PJ (1995) Oxyradical generation after resuscitation of hemorrhagic shock with blood or stroma free hemoglobin. Artif Cells Blood Substit Immob Biotechnol J 23:631–645CrossRef
Bucci E (2011) Basic science offers a challenge for developing hemoglobin based oxygen carriers into therapeutic agent. Artif Cells Blood Substit Immob Biotechnol J 39:206–213CrossRef
Bucci E (2013) Evidences regarding some pharmacologic characteristics of haemoglobin based oxygen carriers. In: Chang TMS (ed) Selected topics in nanomedicine. World Science Publisher/Imperial College Press, UK
Buehler PW, Haney CR, Gulati A, Ma L, Hsia CJ (2004) Polynitroxyl hemoglobin: a pharmacokinetic study of covalently bound nitroxides to hemoglobin platforms. Free Radical Biol Med 37(1):124–135CrossRef
Bunn HF, Jandl JH (1968) The renal handling of hemoglobin. Trans Assoc Am Phys 81:147
Burhop KE, Estep TE (2001) Hb induced myocardial lesions. Artf Cells Blood Subst Immob Biotech 29:101–106
Chang TMS (1957) Hemoglobin corpuscles-report of a research project for honours physiology. Medical Library, McGill University. Also reprinted in full in Chang’s 2007 Monograph on Artificial Cells
Chang TMS (1965) Semipermeable aqueous microcapsules. Ph.D. Thesis, McGill University
Chang TMS (1971) Stabilisation of enzymes by microencapsulation with a concentrated protein solution or by microencapsulation followed by cross-linking with glutaraldehyde. Biochem Biophys Res Commun 44:1531–1536CrossRef
Chang TMS (1976) Biodegradable semipermeable microcapsules containing enzymes hormones, vaccines, and other biologicals. J Bioeng 1:25–32
Chang TMS (2005) Therapeutic applications of polymeric artificial cells. Nat Rev Drug Discov 4:221–235CrossRef
Chang TMS (2007) Artificial cells: biotechnology, nanotechnology, blood substitutes, regenerative medicine, bioencapsulation, cell/stem cell therapy. World Scientific Publisher/Imperial College Press, UK p 435 www.​artcell.​mcgill.​ca
Chang TMS (2009) Nanobiotechnology for hemoglobin based blood substitutes. Crit Care Clin 25:373–382CrossRef
Chang TMS (2010) Blood replacement with engineered hemoglobin and hemoglobin nanocapsules. Wiley Interdiscipl Rev Nanomed Nanobiotechnol 2:418–430CrossRef
Chang TMS (2011) Nanobiotechnology-based blood substitutes and the cardiovascular systems in transfusion medicine. In: Nanomedicine and cardiovascular system. TFM Publishing, UK pp 77–98
Chang TMS (2012) Artificial red blood cells, oxygen carriers, oxygen therapeutics to artificial cells and nanomedicine and beyond. Artif Cells Blood Substit Biotechnol J 40(3):197–199
Chang EJ, Lee TH, Mun KC et al (2004) Effects of polyhemoglobin-antioxidant enzyme complex on ischemia-reperfusion in kidney. Trans Proc 36: 1952–1954
Chang TMS, Powanda D, Yu WP (2003) Analysis of polyethyleneglycol polylactide nano-dimension artificial red blood cells in maintaining systemic hemoglobin levels and prevention of methemoglobin formation. Artif Cells Blood Substit Biotechnol 31:231–248CrossRef
Chang TMS, Poznansky MJ (1968) Semipermeable microcapsules containing catalase for enzyme replacement in acatalsaemic mice. Nature 218:242–245CrossRef
D’Agnillo F, Chang TMS (1998) Polyhemoglobin-superoxide dismutasecatalase as a blood substitute with antioxidant properties. Nat Biotechnol 16:667–671CrossRef
Deamer DW, Bangham AD (1976) Large-volume liposomes by an ether vaporization method. Biochem Biophys Acta 443:629–634
DeVenuto F, Zegna AI (1982) Blood exchange with pyridoxalated–polymerized hemoglobin. Surg Gynecol Obstet 155:342
Djordjevich L, Miller IF (1980) Synthetic erythrocytes from lipid encapsulated hemoglobin. Exp Hematol 8:584
Doherty DH, Doyle MP, Curry SR et al (1998) Rate of reaction with nitric oxide determine the hypertensive effect of cell free hemoglobin. Nat Biotechnol 16: 672–676
Dudziak R, Bonhard K (1980) The development of hemoglobin preparations for various indications. Anesthesist 29:181
Farmer MC, Rudolph AS, Vandegriff KD, Havre MD, Bayne SA, Johnson SA (1988) Lipsome–encapsulated hemoglobin: oxygen binding properties and respiratory function. Biomat Artif Cells Artif Organs 16:289–299
Feola MH, Gonzalez H, Canizaro PC, Bingham D (1983) Development of bovine stroma–free hemoglobin solution as a blood substitute. Sur Gynecol Obstet 157:399
Fratantoni JC (1994) Points to consider on efficacy evaluation of hemoglobin and perfluorocarbon based oxygen carriers. Transfusion 34:712–713CrossRef
Fustier C, Chang TMS (2012) PEG-PLA nanocapsules containing a nanobiotechnological complex of polyhemoglobin-tyrosinase for the depletion of tyrosine in melanoma: preparation and in vitro characterisation 2:1
Gould SA, Sehgal LR, Sehgal HL, Moss GS (1995) The development of hemoglobin solutions as red cell substitutes: hemoglobin solutions. Trans Sci 16:5–17
Gould SA et al (2002) The life-sustaining capacity of human polymerized hemoglobin when red cells might be unavailable. J Am Coll Surg 195:445–452CrossRef
Greenburg AG (2013) The clinical development of hemopure® : a selective commentary. In: Chang RMS (ed) Selected topics in nanomedicine. World Science Publisher/Imperial College Press, UK
Greenburg AG, Kim HW (1992) Evaluating new red cell substitutes: a critical analysis of toxicity models. Biomat Artif Cells Immob Biotechnol 20:575–581
Greenburg AG, Pitman A, Pearce LB, Kim HW (2008) Clinical contextualization and the assessment of adverse events in hboc trials. Artif Cells Blood Substit Biotechnol 36: 477–486
Han JQ, Yu MH, Dai M, Li HW, Xiu RJ, Liu Q (2012) Decreased expression of MDR1 in PEG-conjugated hemoglobin solution combined cisplatin treatment in a tumor xenograft model. Artif Cells Blood Substit Biotechnol 40:239–244
Hoffman SJ, Looker DL, Roehrich JM et al (1990) Expression of fully functional tetrameric human hemoglobin in Escherichia coli. Proc Natl Acad Sci USA 87:8521–8525
Hsia JC, Song DL, Er SS, Wong LTL (1992) Pharmacokinetic studies on a raffinose– polymerized human hemoglobin in the rat. Biomat Artif Cells Immob Biotechnol 20:587–596
Iwashita Y (1992) Relationship between chemical properties and biological properties of pyridoxalated hemoglobin–polyoxyethylene. Biomat Artif Cells Immob Biotechnol 20:299–308
Jahr JS, Mackenzie C, Pearce LB, Pitman A, Greenburg AG (2008) HBOC-201 as an alternative to blood transfusion: efficacy and safety evaluation in a multicenter phase III trial in elective orthopaedic surgery. J Trauma 64:1484–1497CrossRef
Jia YP, Alayash AI (2013) Molecular basis of haptoglobin and hemoglobin complex formation and protection against oxidative stress and damage. In: Chang TMS (ed) Selected topics in nanomedicine. World Science Publisher/Imperial College Press, UK
Keipert P, Chang TMS (1987) In–vivo effects of total and partial isovolemic exchange transfusion in fully conscious rats using pyridoxalated polyhemoglobin solution as a colloidal oxygen–delivery blood substitute. Vox Sanguinis 53:7–14CrossRef
Keipert PE, Minkowitz J, Chang TMS (1982). Cross–linked stroma–free polyhemoglobin as a potential blood substitute. Int J Artif Organs 5(6):383
Kim HW, Greenburg AG (1997) Ferrous hemoglobin scavenging of endothelium derived nitric oxide is a principal mechanism for hemoglobin mediated vasoactivities in isolated rat thoracic aorta transfusion. Artif Cells Blood Substit Immob Biotechnol Int J 25:121–134CrossRef
Klein HG (2000) The prospects for red-cell substitutes. N Engl J Med. 342(22):1666–68
Kobayashi K, Tsuchida E Horinouchi H (ed) (2005) Artificial oxygen carriers. Springer, Tokyo
Li XZ (2005) Determination of the molecular weight distribution of PEGylated bovine hemoglobin (PEG-bHb). Artif Cells Blood Substit Biotechnol Int J 33:13–28CrossRef
Li T, Yu R, Zhang HH, Liang WG, Yang XM, Yang CM (2006) A method for purification and viral inactivation of human placenta hemoglobin. Artif Cells Blood Substit Biotechnol Int J
Liu ZC, Chang TMS (2008a) Effects of PEG-PLA-nano artificial cells containing hemoglobin on kidney function and renal histology in rats Artificial Cells. Blood Substit Biotechnol 36:421–430CrossRef
Liu ZC, Chang TMS (2008b) Long term effects on the histology and function of livers and spleens in rats after 33 % top loading of PEG-PLA-nano artificial red blood cells. Artif Cells Blood Substit Biotechnol 36:513–524CrossRef
Liu Q, Xiu RJ (2008) Proceedings of the 11th ISBS symposium at Peking union medical college, Chinese academy of medical sciences. Artif Cells Blood Substit Biotechnol Int J 36(3):169–293
Looker D, Brown D A, Cozart P et al (1992) A human recombinant hemoglobin designed for use as a blood substitute. Nature 356: 258–260
Ma L, Hsia CJC (2013) Polynitroxylated hemoglobin as a multifunctional therapeutic for critical care and transfusion medicine. In: Chang TMS (ed) Selected topics in nanomedicine. World Science Publisher/Imperial College Press, UK
Mazurier C, Douay L, Lapillonne H (2011) Red blood cells from induced pluripotent stem cells: hurdles and developments. Curr Opin Hematol 18:249–253CrossRef
Moore E, Moore FA, Fabian TC, Bernard AC, Fulda GJ, Hoyt DB et al (2009) Human polymerized hemoglobin for the treatment of hemorrhagic shock when blood is unavailable: the USA multicenter trial. J Am Coll Surg 208:1–13CrossRef
Moss GS, Gould SA, Sehgal LR, Sehgal HL, Rosen AL (1988) Hemoglobin solution—from tetramer to polymer. Biomat Artif Cells Artif Organs 16:57–69
Mozzarelli A (2010) Proceedings of the 12th ISBS symposium. Artif Cells Blood Subst Biotechnol Int J 38(6):295–342
Nadithe V, Bae YH (2011a) Hemoglobin conjugates with antioxidant enzymes (hemoglobin-superoxide dismutase-catalase) via poly(ethylene glycol) crosslinker for protection of pancreatic beta RINM5F cells in hypoxia. Tissue Eng 17:2453–2462CrossRef
Nadithe V, Bae YH (2011b) Hemoglobin conjugates with antioxidant enzymes (hemoglobin-superoxide dismutase-catalase) via poly(ethylene glycol) crosslinker for protection of pancreatic beta RINm5F cells in hypoxia. Tissue Eng 17:2453–2462CrossRef
Natanson C, Kern SJ, Lurie P, Banks SM, Wolfe SM (2008) Cell-free hemoglobin-based blood substitutes and risk of myocardial infarction and death: a meta-analysis. JAMA 299:2304–2312CrossRef
Park YK, Abuchowski A, Davis S, Davis F (1981) Pharmacology of Escherichia coli-L-asparaginase polyethylene glycol adduct. Anticancer Res 1:373–376
Pearce LB, Gawryl MS (1998) Overview of preclinical and clinical efficacy of Biopure’s HBOCs. In: Chang TMS (ed) Blood substitutes: principles, methods, products and clinical trials, vol 2. Karger, Basel, pp 82–98
Perutz MF (1980) Stereochemical mechanism of oxygen transport by hemoglobin. Proc R Soc Lond B 208:135CrossRef
Philips WT, Klpper RW, Awasthi VD, Rudolph AS, Cliff R, Kwasiborski VV, Goins BA (1999) Polyethylene glyco-modified liposome-encapsulated Hb: a long circulating red cell substitute. J Pharm Exp Therapeutics 288:665–670
Powanda D, Chang TMS (2002) Cross-linked polyhemoglobin-superoxide dismutase-catalase supplies oxygen without causing blood brain barrier disruption or brain edema in a rat model of transient global brain ischemia-reperfusion. Artif Cells Blood Substit Immobil Biotechnol 30:25–42
Przybelski R, Blue J, Nanvaty M, Goldberg C, Estep T, Schmitz T (1996) Clinical studies with diaspirin cross-linked hemoglobin solution (DCLHb™): a review and update. Artif Cells Blood Substit Immob Biotechnol Int J 24:407
Rabiner SF, Helbert JR, Lopas H, Friedman LH (1967) Evaluation of stroma free hemoglobin solution as a plasma expander. J Exp Med 126:1127
Razack S, D’Agnillo F, Chang TMS (1997) Crosslinked hemoglobin-superoxide dismutase-catalase scavenges free radicals in a rat model of intestinal ischemia-reperfusion injury. Artif Cells Blood Substit Immob Biotechnology Int J 25:181–192CrossRef
Robinson MF, Dupuis NP, Kusumoto T, Liu F, Menon K, Teicher BA (1995) Increased tumor oxygenation and radiation sensitivity in two rat tumors by a hemoglobin-based oxygen carrying preparation. Artif Cells Blood Substit Immob Biotechnol Int J 23:431–438
Rousselot M, Delpy E, DLRochelle C, Lagente V, Pirow R, Rees JF, Hagege A, LeGuen D, Hourdez S, Zal F (2006) Arenicola marina extracellular hemoglobin: a new promising blood substitute. Biotechnol J 1(3):333–45
Rudolph AS (1994) Encapsulated hemolgobin: current issues and future goals. Artif Cells Blood Substit Immob Biotechnol Int J 22:347–360
Sakai H (2013) Biocompatibility of a highly concentrated fluid of hemoglobin-vesicles as a transfusion alternative. In: Chang TMS (ed) Selected topics in nanomedicine. World Science Publisher/Imperial College Press, UK
Savitsky JP, Doozi J, Black J, Arnold JD (1978) A clinical safety trial of stroma free hemoglobin. Clin Pharm Ther 23:73
Seetharama A, Acharya, Amy G, Tsai, Intaglietta M (2013) EAF PEG hemoglobins: novel class of non-hypertensive resuscitation fluids: simplicity and advantages of extension arm chemistry for PEGylation. In: Chang TMS (ed) Selected topics in nanomedicine. World Science Publisher/Imperial College Press, UK
Sehgal LR, Rosen AL, Gould SA, Sehgal HL, Moss GS (1983) Preparation and in vitro characteristics of polymerized pyridoxalated hemoglobin. Transfusion 23:158
Sheng Y, Yuan Y, Liu C, Tao X, Shan X, Xu F (2009) In vitro macrophage uptake and in vivo biodistribution of PLA–PEG nanoparticles loaded with hemoglobin as blood substitutes: effect of PEG content. J Mat Sci Mat Med 20(9):1881–1891CrossRef
Shoemaker S, Gerber SM, Evans G, Paik L, Scoggin C (Somatogen Co.USA) (1994) Initial clinical experience with a rationally designed genetically engineered recombinant human hemoglobin. Artif Cells Blood Substit Immob Biotechnol Int J 22: 457–465
Shorr RG, Viau AT, Abuchowski A (1996) Phase 1B safety evaluation of PEG hemoglobin as an adjuvant to radiation therapy in human cancer patients. Artif Cells Blood Substit Immob Biotechnol Int J 24:407
Simoni J, Simoni G, Lox CD, Prien SD, Shires GT(1997). Modified hemoglobin solution with desired pharmacological properties does not activate nuclear transcription factor NF-Kappa B in human vascular endothelial cells. Artif Cells Blood Substit Immob Biotechnol Int J 25:193–210
Sims C, Seigne P, Menconi M, Monarca J, Barlow C, Pettit J, Puyana JC (2001) Skeletal muscle acidosis correlates with the severity of blood volume loss during shock and resuscitation. J Trauma 51:1137–1146CrossRef
Tam SC, Blumenstein J, Wong JT (1976) Dextran hemoglobin. Proc Natl Acad USA 73:2128
Teicher BA (1995) An overview on oxygen-carriers in cancer therapy. Artif Cells Blood Substit Immob Biotechnol Int J 23:395–405CrossRef
Tsuchida E (ed) (1998) Blood substitutes: present and future perspectives. Elsevier, Amsterdam
Tsuchida E, Sakai H, Horinouchi H, Kobayashi K (2006) Artif Cells Blood Substit Immob Biotechnol Int J 34:581–588
Walder JA, Zaugg RH, Walder RY, Steele JM, Klotz IM (1979) Diaspirins that cross–link alpha chains of hemoglobin: bis(3,5–dibromosalicyl) succinate and bis(3,5–dibormosalicyl) fumarate. Biochemistry 18:4265–4270
Van der Linden P, Tadeusz SG, David J, Rene´ JH, Jan CS, _ David P, Ivo K, Andrzej ZG, Bengt F, Peter EK, Yun JH, Howard L (2011) A Double-Blind, Randomized, Multicenter Study of MP4OX for Treatment of Perioperative Hypotension in Patients Undergoing Primary Hip Arthroplasty Under Spinal Anesthesia. Anesth Analg 112:759–773
Wang Y et al (2012) Polymerized human placenta hemoglobin (PolyPHb) attenuates myocardial infarction injury in rats. Artif Cells Blood Substit Immobil Biotechnol 40(1–2):7–13CrossRef
Wei G, Bian YZ, Chang TMS (2013) PLA-PEG nanoencapsulated nano artificial red blood cells that act as O2 and CO2 carrier with enhanced antioxidant activity: polyhemoglobin-superoxide dismutase-catalase-carbonic anhydrase. J Artif Cells Nanomed Biotechnol (in press)
Winslow RM (ed) (2006) Blood substitutes. Academic Press, Amsterdam
Wong JT (1988) Rightshifted dextran-hemoglobin as blood substitute. Biomater Artif Cells Artif Organs 16:237–245
Wong BL Kwok SY (2011) Method for the preparation of a heat stable oxygen carrier-containing pharmaceutical composition. US Patent 7(932):356
Wong N, Chang TMS (2007) Polyhemoglobin-fibrinogen: a novel blood substitutes with platelet-like activity for extreme hemodilution. Artif Cells Blood Substit Biotechnol 35:481–489
Wong BLS, Kwok SY, Lau SH (2011) Treatment methods using a heat stable oxygen carrier-containing pharmaceutical composition. November 2011: US 8048856
Yabuki A, Yamaji K, Ohki H, Iwashita Y (1990) Characterization of a pyridoxylated hemoglobin-polyoxyethylene conjugate as a physiologic oxygen carrier. Transfusion 30:516–20
Yu BL, Chang TMS (2004) In vitro and in vivo effects of polyhemoglobintyrosinase on murine B16F10 melanoma. Melanoma Res J 14:197–202CrossRef
Yu B, Shahid M, Egorina EM, Sovershaev MA, Raher MJ, Lei C, Wu MX, Bloch KD, Zapol WM (2010) Endothelial dysfunction enhances vasoconstriction due to scavenging of nitric oxide by a hemoglobin-based oxygen carrier. Anesthesiology 112:586–594CrossRef
Zapol W (2012) Proceedings of the 13th ISBS symposium at mass general hospital of Harvard medical school. Artif Cells Blood Substit Biotechnol Int J 40(3)
Zhang X, Liu C, Yuan Y, Zhang S, Shan X, Sheng Y, Xu F (2008). Key parameters affecting the initial leaky effect of hemoglobin-loaded nanoparticles are blood substitutes. J Mater Sci Mater Med. 19(6):2463–70
Zhu YJW, Chen C (2013) Glutaraldehyde polymerized porcine haemoglobin. In: Chang TMS (ed) Selected topics in nanomedicine. World Science Publisher/Imperial College Press, UK
Zhu XL, Chu W, Wang T, Wang F, Fan D, Dan N, Chen C (2007) Variations in dominant antigen determinants of glutaraldehyde polymerized human, bovine and porcine hemoglobin. Artif Cells Blood Substit Biotechnol 35:518–532CrossRef
Zuck TF (1994) In: Winslow R (ed) Difficulties in demonstrating efficacy of blood substitutes. Artif Cells Blood Substit Immob Biotechnol Int J 22: 945–954
Metadata
Title
From Hemoglobin Based Oxygen Carrier to Oxygen Therapeutics, Blood Substitutes, Nanomedicine and Artificial Cells
Author
Thomas Ming Swi Chang
Copyright Year
2013
Publisher
Springer Berlin Heidelberg
Book
Hemoglobin-Based Oxygen Carriers as Red Cell Substitutes and Oxygen Therapeutics

Print ISBN: 978-3-642-40716-1

Electronic ISBN: 978-3-642-40717-8

Copyright Year: 2013

DOI
https://doi.org/10.1007/978-3-642-40717-8_1

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