Artificial oxygen carrier: its front line

Kobayashi, Kenichi; Tsuchida, E.; Horinouchi, Hirohisa

doi:10.1590/s0036-46652005000100010

Cited by 4 publications

(5 citation statements)

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“…Our group has studied safety issues of HbV extensively [1,3,[7][8][9]14,15]; no deteriorative or irreversible side effects have been observed after HbV infusion. Therefore, it was not surprising for us that all the rats survived one year after receiving intravenous bolus infusion of HbV (20 ml=kg) with no pathological abnormality in the lung, even though this was the first study to confirm one-year survival after HbV infusion.…”

Section: Discussionmentioning

confidence: 99%

“…Phospholipid vesicles or liposomes encapsulating hemoglobin (Hbvesicles, HbV) can serve as an O 2 carrier with comparable ability to that of red blood cells (RBC) [1][2][3][4][5]. Advantages of the Hb-based O 2 carriers (HBOCs) are the absence of blood-type antigens and transmission of known and unknown blood-borne diseases, the possibility of improving rheological properties of blood flow according to patients' needs, and stable long-term storage [6].…”

Section: Introductionmentioning

confidence: 99%

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One-Year Observation of Wistar Rats after Intravenous Infusion of Hemoglobin-Vesicles (Artificial Oxygen Carriers)

Sakai

Tsuchida

Horinouchi

et al. 2007

Artificial Cells, Blood Substitutes, and Biotechnology

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Hemoglobin-vesicles (HbV) or liposome-encapsulated Hb are artificial oxygen carriers. Our previous studies of the bolus infusion of HbV into Wistar rats showed that HbV was captured by the reticuloendothelial system from the blood stream and degraded completely with no deteriorative effect for 2 weeks. However, one authority on artificial organs research suggested conducting a one-year observation because he experienced, with one lipid-emulsified perfluorocarbon (PFC), that rats died within one year from a pulmonary abnormality after receiving the PFC emulsion due to the unstable dispersion state (personal communication). We thought this would never happen for HbV because the dispersion state of HbV is stable with PEG-modification. To confirm this, we made one-year observations after HbV infusion as suggested. Five male Wistar rats intravenously received 20 ml/kg HbV suspended in saline ([Hb] = 10 g/dL). They were housed in separated cages and provided with food and water ad libitum. All rats survived one year, and were apparently healthy. Their body weights (821+/-75 g) reflected obesity from their confinement in small cages. No histopathological abnormality was found in the lung. Plasma biochemical analyses showed overall normal organ functions. In our previous report, plasma lipid levels increased transiently at 1 or 2 days; then they reverted to the control level at 7 days. One year later, the rats showed much higher plasma lipid levels, a symptom of hyperlipidemia that is attributable to obesity and aging. It seemed the transient increases at the early days had no impact compared with the levels of hyperlipemia of the old rats.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

One-Year Observation of Wistar Rats after Intravenous Infusion of Hemoglobin-Vesicles (Artificial Oxygen Carriers)

Sakai

Tsuchida

Horinouchi

et al. 2007

Artificial Cells, Blood Substitutes, and Biotechnology

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“…[5][6][7] They can be divided into three generations. [8][9][10][11][12][13] The first generation was simply modified hemoglobin such as polyhemoglobin and conjugated hemoglobin. Because modified hemoglobin exists in the blood in almost the naked state and stays in direct contact with plasma, it gets oxidized and loses its oxygen-binding ability rapidly.…”

Section: Introductionmentioning

confidence: 99%

Oxygen Carrier Based on Hemoglobin/Poly(l-lysine)-block-poly(l-phenylalanine) Vesicles

et al. 2009

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An oxygen carrier was prepared by encapsulating carbonylated hemoglobin (CO-Hb) molecules into polypeptide vesicles made from poly(L-lysine)-block-poly(L-phenylalanine) (PLL-b-PPA) diblock copolymers in aqueous medium at pH 5.8. The encapsulation was confirmed by confocal laser scanning microscopy (CLSM). The morphology and size of the vesicles were studied by field-emission scanning electron microscopy (ESEM). They had a spherical shape with a mean diameter of about 4 to 5 microm. The encapsulation efficiency of hemoglobin was 40 wt %, and the hemoglobin content in the vesicles was 32 wt %. The CO-Hb encapsulated in the PLL-b-PPA vesicles was more stable than free CO-Hb under ambient conditions. In the presence of a O(2) atmosphere, the CO-Hb in the vesicle could be converted into oxygen-binding hemoglobin (O(2)-Hb) under irradiation of visible light for 2 h. Therefore, the CO-Hb/PLL-b-PPA vesicles are expected to be used as red blood cell substitutes.

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“…Some of them are undergoing clinical trials [1,2]. Advantages of the HBOCs include the absence of blood-type antigenicity and infectious pathogens, and better stability for long-term storage than RBC transfusion [1,3].…”

Section: Introductionmentioning

confidence: 99%

“…Advantages of the HBOCs include the absence of blood-type antigenicity and infectious pathogens, and better stability for long-term storage than RBC transfusion [1,3]. Phospholipid vesicles or liposome encapsulating concentrated human Hb (Hb-vesicle, HbV) have been developed as O 2 carriers [1][2][3][4][5][6]. The HbV cellular structure (particle diameter, ca.…”

Section: Introductionmentioning

confidence: 99%

Hemoglobin-Vesicles as a Transfusion Alternative

Tsuchida

Sakai

Horinouchi

et al. 2006

Artificial Cells, Blood Substitutes, and Biotechnology

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Phospholipid vesicles or liposomes encapsulating purified and concentrated human hemoglobin (Hb-vesicle, HbV) have been developed as a transfusion alternative. They are void of blood-type antigens and infectious viruses; they are stable and suitable for long-term storage. The cellular structure of HbV (particle diameter, ca. 250 nm) prevents direct contact of Hb with the blood components and the endothelial lining shielding cells from the side effects of Hb molecules. Microcirculatory observations show that the cellular structure of HbV is important to control reactions with endothelium-derived vasorelaxation factors. Animal studies of extreme hemodilution and resuscitation from hemorrhagic shock attest to the sufficient oxygen transporting capacity of HbV. Studies of biodistribution and metabolism reveal that HbVs are captured eventually in the reticuloendothelial system, and degraded within one week. In a joint collaboration partnership of academia, a biotech venture company and a corporation, we plan to produce HbV with good manufacturing practices, and to start preclinical and, finally, clinical trials within a few years.

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Artificial oxygen carrier: its front line

Cited by 4 publications

References 0 publications

One-Year Observation of Wistar Rats after Intravenous Infusion of Hemoglobin-Vesicles (Artificial Oxygen Carriers)

One-Year Observation of Wistar Rats after Intravenous Infusion of Hemoglobin-Vesicles (Artificial Oxygen Carriers)

Oxygen Carrier Based on Hemoglobin/Poly(l-lysine)-block-poly(l-phenylalanine) Vesicles

Hemoglobin-Vesicles as a Transfusion Alternative

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