On the use of ringer‐locke solutions containing hemoglobin as a substitute for normal blood in mammals

Amberson, William R.; Flexner, James Thomas; Steggerda, F. R.; Mulder, Arthur G.; Tendler, Morton J.; Pankratz, David S.; Laug, Edwin P.

doi:10.1002/jcp.1030050309

Cited by 68 publications

(15 citation statements)

References 21 publications

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“…There is an urgent need for universal blood substitutes due to the limited supply of fresh blood, the finite shelf life of blood, and the possibility of infections caused by blood‐borne pathogens. Cell‐free hemoglobin (Hb) solutions have been evaluated as potential emergency blood substitutes as early as 1943 by Amberson et al (1) and continue to be widely studied even now. There are several types of cell‐free Hb solutions: tetrameric Hb composed of two αβ dimers held together by noncovalent bonds, polymeric Hb produced by intermolecular cross‐linking of tetrameric Hb, and conjugated Hb produced by cross‐linking individual Hb molecules to polymers (2 − 6).…”

Section: Introductionmentioning

confidence: 99%

Determination of Size Distribution and Encapsulation Efficiency of Liposome‐Encapsulated Hemoglobin Blood Substitutes Using Asymmetric Flow Field‐Flow Fractionation Coupled with Multi‐Angle Static Light Scattering

Arifin

Palmer

2003

Biotechnology Progress

100

140

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In this study, we investigated the size distribution, encapsulation efficiency, and oxygen affinity of liposome-encapsulated tetrameric hemoglobin (LEHb) dispersions and correlated the data with the variation in extruder membrane pore size, ionic strength of the extrusion buffer, and hemoglobin (Hb) concentration. Asymmetric flow field-flow fractionation (AFFF) in series with multi-angle static light scattering (MASLS) was used to study the LEHb size distribution. We also introduced a novel method to measure the encapsulation efficiency using a differential interferometric refractive index (DIR) detector coupled to the AFFF-MASLS system. This technique was nondestructive toward the sample and easy to implement. LEHbs were prepared by extrusion using a lipid combination of dimyristoyl-phosphatidylcholine, cholesterol, and dimyristoyl-phosphatidylglycerol in a 10:9:1 molar ratio. Five initial Hb concentrations (50, 100, 150, 200, and 300 mg Hb per mL of buffer) extruded through five different membrane pore diameters (400, 200, 100, 80, and 50 nm) were studied. Phosphate buffered saline (PBS) and phosphate buffer (PB) both at pH 7.3 were used as extrusion buffers. Despite the variation, extrusion through 400-nm pore diameter membranes produced LEHbs smaller than the pore size, extrusion through 200-nm membranes produced LEHbs with diameters close to the pore diameter, and extrusion through 100-, 80-, and 50-nm membranes produced LEHbs larger than the pore sizes. We found that the choice of extrusion buffer had the greatest effect on the LEHb size distribution compared to either Hb concentration or extruder membrane pore size. Extrusion in PBS produced larger LEHbs and more monodisperse LEHb dispersions. However, LEHbs extruded in PB generally had higher Hb encapsulation efficiencies and lower methemoglobin (metHb) levels. The choice of extrusion buffer also affected how the encapsulation efficiency correlated with Hb concentration, extruder pore size, and the metHb level. The most optimum encapsulation efficiency and amount of Hb entrapped were achieved at the highest Hb concentration and the largest pore size for both extrusion buffers (62.38% and 187.14 mg Hb/mL of LEHb dispersion extruded in PBS, and 69.98% and 209.94 mg Hb/mL of LEHb dispersion extruded in PB). All LEHbs displayed good oxygen-carrying properties as indicated by their P(50) and cooperativity coefficients. LEHbs extruded in PB had an average P(50) of 23.04 mmHg and an average Hill number of 2.29, and those extruded in PBS had average values of 27.25 mmHg and 2.49. These oxygen-binding properties indicate that LEHbs possess strong potential as artificial blood substitutes. In addition, the metHb levels in PB-LEHb dispersions are significantly low even in the absence of antioxidants such as N-acetyl-L-cysteine.

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Section: Introductionmentioning

confidence: 99%

Determination of Size Distribution and Encapsulation Efficiency of Liposome‐Encapsulated Hemoglobin Blood Substitutes Using Asymmetric Flow Field‐Flow Fractionation Coupled with Multi‐Angle Static Light Scattering

Arifin

Palmer

2003

Biotechnology Progress

100

140

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“…Obtaining universal and safe blood substitutes has been in the focus for the last 80 years, since the first report was published (Amberson et al, ) regarding the utilization of stroma free hemoglobin solutions as an alternative for blood transfusions (Li et al, ). However, it was not until the 1980s when serious efforts were made, mainly due to the increasing concern regarding HIV, hepatitis C and other harmful viruses, present in the donor blood (Chang, ).…”

Section: Introductionmentioning

confidence: 99%

Engineering the oxygen sensing regulation results in an enhanced recombinant human hemoglobin production by Saccharomyces cerevisiae

Martínez

Liu

Petranović

et al. 2014

Biotech & Bioengineering

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Efficient production of appropriate oxygen carriers for transfusions (blood substitutes or artificial blood) has been pursued for many decades, and to date several strategies have been used, from synthetic polymers to cell-free hemoglobin carriers. The recent advances in the field of metabolic engineering also allowed the generation of different genetically modified organisms for the production of recombinant human hemoglobin. Several studies have showed very promising results using the bacterium Escherichia coli as a production platform, reporting hemoglobin titers above 5% of the total cell protein content. However, there are still certain limitations regarding the protein stability and functionality of the recombinant hemoglobin produced in bacterial systems. In order to overcome these limitations, yeast systems have been proposed as the eukaryal alternative. We recently reported the generation of a set of plasmids to produce functional human hemoglobin in Saccharomyces cerevisiae, with final titers of active hemoglobin exceeding 4% of the total cell protein. In this study, we propose a strategy for further engineering S. cerevisiae by altering the oxygen sensing pathway by deleting the transcription factor HAP1, which resulted in an increase of the final recombinant active hemoglobin titer exceeding 7% of the total cellular protein.

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“…Six years before the World War II (WW II) theater began, 1 William R. Amberson et al . (1933) demonstrated that bovine red blood cell (bRBC) hemolysates can transport oxygen (O 2 ) and sustain life when transfused into mammals 2,3 . Prior to this, Sellards and Minot (1916) formulated hemoglobin (Hb) solutions from lysed RBCs for infusion into patients with anemia 4 .…”

Section: Introductionmentioning

confidence: 99%

Novel strategies for transporting cellular hemoglobin‐based oxygen carriers in the systemic circulation

Harris

Palmer

2007

Transfus Alt Transfus Med

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SUMMARY This review focuses on innovative chemical and biomolecular design strategies for engineering cellular hemoglobin‐based oxygen carriers with prolonged systemic circulatory half‐lives. Traditional lipid formulations used in the self‐assembly of liposome encapsulated hemoglobin dispersions are discussed in light of newly designed liposome, nanoparticle and polymersome encapsulated hemoglobin dispersions. The clinical transfusion potential of these cellular HBOCs is discussed in terms of key design parameters such as: particle size distribution, hemoglobin encapsulation efficiency, methemoglobin level, oxygen affinity, cooperativity coefficient, circulation kinetics and biodistribution.

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On the use of ringer‐locke solutions containing hemoglobin as a substitute for normal blood in mammals

Cited by 68 publications

References 21 publications

Determination of Size Distribution and Encapsulation Efficiency of Liposome‐Encapsulated Hemoglobin Blood Substitutes Using Asymmetric Flow Field‐Flow Fractionation Coupled with Multi‐Angle Static Light Scattering

Determination of Size Distribution and Encapsulation Efficiency of Liposome‐Encapsulated Hemoglobin Blood Substitutes Using Asymmetric Flow Field‐Flow Fractionation Coupled with Multi‐Angle Static Light Scattering

Engineering the oxygen sensing regulation results in an enhanced recombinant human hemoglobin production by Saccharomyces cerevisiae

Novel strategies for transporting cellular hemoglobin‐based oxygen carriers in the systemic circulation

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