Red blood cell replacement, or nanobiotherapeutics with enhanced red blood cell functions?

Chang, Thomas Ming Swi

doi:10.3109/21691401.2015.1047557

Cited by 12 publications

(14 citation statements)

References 38 publications

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“…SFHb contains haemoglobin and red blood cell enzymes including CAT, SOD and CA. The enzyme extracted had been established previously [24,25]. 300 ml bovine SFHb (Hb concentration: 9g/dL) is placed in a beaker on ice.…”

Section: Bovine Enzyme Extraction and MIX With Bovine Stroma-free Haementioning

confidence: 99%

“…To enhance the red blood cell enzymes, commercial CAT, SOD and CA are added for the preparation of poly-[Hb-CAT-SOD-CA] [20][21][22][23]. For avoiding the high cost of commercial enzymes, a cost-effective novel enzyme extraction method has been established to obtain these three enzymes from SFHb simultaneously [24,25]. This avoids the need for expensive commercial enzymes and allows the large-scale production of poly-[Hb-CAT-SOD-CA] in the future.…”

Section: Introductionmentioning

confidence: 99%

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Long term safety and immunological effects of a nanobiotherapeutic, bovine poly-[hemoglobin-catalase-superoxide dismutase-carbonic anhydrase], after four weekly 5% blood volume top-loading followed by a challenge of 30% exchange transfusion

Guo

Chang

2018

Artificial Cells, Nanomedicine, and Biotechnology

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The long-term safety and immunological effects of bovine poly-[haemoglobin-catalase-superoxide dismutase-carbonic anhydrase] in rats are studied by four-weekly 5% blood volume top-loading infusions followed by 30% blood volume exchange transfusion. There is no significant difference in growth, biochemistry and blood pressure between the control group receiving lactated ringer solution and those receiving the bovine poly-[haemoglobin-catalase-superoxide dismutase-carbonic anhydrase]. There is no significant change in mean arterial pressures (MAP) before and after each weekly top-loading infusion. After both the four weekly top-loading and the 30% exchange transfusions, the following safety and immune response evaluations are carried out. These include general studies on Ouchterlony double diffusion, total IgG and IgM, and complement activation. This is followed by quantitative measurements of specific antibodies against each of the following bovine components: Hb, CAT, SOD and CA in bovine poly-[haemoglobin-catalase-superoxide dismutase-carbonic anhydrase]. After the four weekly top-loading, each rat received a challenge of 30% blood volume exchange transfusion. The MAP, histamine and tryptase levels are tested before and after the 30% exchange transfusion. There are no anaphylactic reactions as shown by the MAP or histamine and tryptase. The results showed no safety problem nor adverse immune responses. All the rats survived when followed for one week after the 30% exchange transfusion.

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Section: Bovine Enzyme Extraction and MIX With Bovine Stroma-free Haementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Long term safety and immunological effects of a nanobiotherapeutic, bovine poly-[hemoglobin-catalase-superoxide dismutase-carbonic anhydrase], after four weekly 5% blood volume top-loading followed by a challenge of 30% exchange transfusion

Guo

Chang

2018

Artificial Cells, Nanomedicine, and Biotechnology

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“…The first generation blood substitute is based on the basic principle of polyhemoglobin (PolyHb) (Chang 1964(Chang , 1971). This has been developed independently by others and has undergone extensive clinical trials (Alayash et al 2007, Bian et al 2013, Chang 2014, Chang 2015, Jahr et al 2008, Kim and Greenburg 2014and Zhao et al 2014. It is already approved for routine clinical use in countries where HIV in donor blood is still a major problem.…”

Section: Introductionmentioning

confidence: 99%

Temperature stability of Poly-[hemoglobin-superoxide dismutase-catalase-carbonic anhydrase] in the form of a solution or in the lyophilized form during storage at −80 °C, 4 °C, 25 °C and 37 °C or pasteurization at 70 °C

Bian

Guo

Chang

2015

Artificial Cells, Nanomedicine, and Biotechnology

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Polyhemoglobin-superoxide dismutase-catalase-carbonic anhydrase (Poly-[Hb-SOD-CAT-CA]) contains all three major functions of red blood cells (RBCs) at an enhanced level. It transports oxygen, removes oxygen radicals and transports carbon dioxide. Our previous studies in a 90-min 30 mm Hg Mean Arterial Pressure (MAP) sustained hemorrhagic shock rat model shows that it is more effective than blood in the lowering of elevated intracellular pCO 2 , recovery of ST-elevation and histology of the heart and intestine. This paper is to analyze the storage and temperature stability. Allowable storage time for RBC is about 1 d at room temperature and 42 d at 4C. Also, RBC cannot be pasteurized to remove infective agents like HIV and Ebola. PolyHb can be heat sterilized and can be stored for 1 year even at room temperature. However, Poly-[Hb-SOD-CAT-CA] contains both Hb and enzymes and enzymes are particularly sensitive to storage and heat. We thus carried out studies to analyze its storage stability at different temperatures and heat pasteurization stability. Results of storage stability show that lyophilization extends the storage time to 1 year at 4 C and 40 d at room temperature (compared to respectively, 42 d and 1 d for RBC). After the freeze-dry process, the enzyme activities of Poly-[SFHb-SOD-CAT-CA] was 100 ± 2% for CA, 100 ± 2% for SOD and 93 ± 3.5% for CAT. After heat pasteurization at 70 C for 2 h, lyophilized Poly-[Hb-SOD-CAT-CA] retained good enzyme activities of CA 97 ± 4%, SOD 100 ± 2.5% and CAT 63.8 ± 4%. More CAT can be added during the crosslinking process to maintain the same enzyme ratio after heat pasteurization. Heat pasteurization is possible only for the lyophilized form of Poly-[Hb-SOD-CAT-CA] and not for the solution. It can be easily reconstituted by dissolving in suitable solutions that continues to have good storage stability though less than that for the lyophilized form. According to the P50 value, Poly-[SFHb-SOD-CAT-CA] retains its oxygen carrying ability before and after long-term storage.ARTICLE HISTORY

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“…These life‐saving biologics are expected to revolutionize blood banking and transfusion medicine practices. Patients will benefit from having access to readily available pathogen‐free oxygen‐carrying volume expanders with universal compatibility and prolonged storage and at reasonably low price, with assurance that benefits outweigh any potential risks .…”

mentioning

confidence: 99%

“…A new orthogonal Hb purification technology provides complete removal of viruses and prion proteins . Chemical stabilization of Hb molecule along with modulating its oxygen affinity, creating stable polymeric structures with advanced cross‐linkers, decreasing its pro‐oxidative activity by engineering tyrosine electron transfer pathway and protecting heme by conjugation with antioxidants (i.e., GSH, nitroxyl radicals, SOD, catalase, carbonic anhydrase), alleviating its vasoconstrictive potential by protection of beta 93 cysteine (i.e., with 4,4′‐dithiodipyridine), targeted decoration with PEG, pharmacological modification with vasodilators (i.e., ATP, adenosine, NO‐donors), and CO‐saturated products are taking the lead . Classical Hb encapsulation is still in use and has become more advanced.…”

mentioning

confidence: 99%

Artificial Oxygen Carriers: Exactly How Close Are We to an Ultimate Product?

Simoni

2017

Artificial Organs

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Red blood cell replacement, or nanobiotherapeutics with enhanced red blood cell functions?

Cited by 12 publications

References 38 publications

Long term safety and immunological effects of a nanobiotherapeutic, bovine poly-[hemoglobin-catalase-superoxide dismutase-carbonic anhydrase], after four weekly 5% blood volume top-loading followed by a challenge of 30% exchange transfusion

Long term safety and immunological effects of a nanobiotherapeutic, bovine poly-[hemoglobin-catalase-superoxide dismutase-carbonic anhydrase], after four weekly 5% blood volume top-loading followed by a challenge of 30% exchange transfusion

Temperature stability of Poly-[hemoglobin-superoxide dismutase-catalase-carbonic anhydrase] in the form of a solution or in the lyophilized form during storage at −80 °C, 4 °C, 25 °C and 37 °C or pasteurization at 70 °C

Artificial Oxygen Carriers: Exactly How Close Are We to an Ultimate Product?

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