Synthesis and Evaluation of a Prototypal Artificial Red Cell

Abstract

A new process allows microencapsulation of purified human hemoglobin and 2,3-diphosphoglycerate to form neohemocytes. The microcapsule membrane is composed of phospholipids and cholesterol. Neohemocytes are substantially smaller than erythrocytes, contain 15.1 grams per decaliter of hemoglobin, and have a P50 value (the partial pressure of oxygen at which the hemoglobin is half-saturated) of 24.0 torr. All rats given 50-percent exchange transfusions survived with only limited evidence of reversible toxicity. Normal serum glutamate-pyruvate-transaminase values at 1, 7, and 30 days after transfusion were consistent with minimal hepatotoxicity. The concentration of blood urea-nitrogen was elevated by 35 percent after 1 day but returned to normal by day 7. However, histopathology revealed normal kidneys on day 1 as well as on days 7 and 30. Neohemocytes cleared from the circulation of transfused rats with an apparent half-life of 5.8 hours.

Effects of PEG-PLA-nano Artificial Cells Containing Hemoglobin on Kidney Function and Renal Histology in Rats

“…Djordjevich and Miller [4] increased the circulation time further by preparing smaller lipid membrane Hb artificial cells with diameter of about 0.2 micron. One of the next important developments is the incorporation of PEG onto the lipid membrane artificial cells, resulting in useful increases in the circulation time [5]. Ongoing efforts are being carried out in preclinical studies towards clinical trial [6,7].…”

Blood Transfusion or Blood Substitution?

“…This work led eventually to the development of 'hemos omes' in which polymerized SFH was incorporated into cholesterol-phospholipid capsules [19]; preliminary tests using hemosomes dispersed in an albumin-electrolyte solution were conducted in animals with encouraging results [19], While hemosomes showed several attributes of syn thetic red cells, more recent work has been concerned with improving encapsulation techniques and producing non toxic and biodegradable membranes. A significant ad vance in this area was achieved by the development of 'neohemocytes' which are microcapsules containing puri fied human haemoglobin and 2,3-diphosphoglycerate [20]. It has been argued that neohemocytes rather than breathed supplementary oxygen.…”

“…Haemoglobin is an obvious choice as a component of blood substitutes since it can be relatively easily prepared from outdated banked blood. This pro cess involves lysis of washed red cells followed by centri fugation and filtration under pressure; the resultant solu tions can be conveniently stored in a lyophilized condi tion [15], Despite their adequacy in terms of oxygen hemosomes qualify as prototypal artificial red cells since in addition to the characteristics above, they also meet other essential specifications including lack of degrada tion of encapsulated haemoglobin and a physiologicallyacceptable oxygen-affinity [20]. Neohemocytes have also been tested in vivo in animal experiments [20] but are not yet available for assessment in man.…”

Evaluation of human hemoglobin vesicle as an oxygen carrier: recovery from hemorrhagic shock in rabbits

“…In this study, we assessed the oxygen-transporting efficacy and safety of the newly developed hemoglobin encapsulated in liposomes together with a metHb reduction system to overcome the autooxidation of Hb. Stroma-free hemoglobin (SFH) solution was prepared from outdated human red blood cells (RBC, Japan Red Cross) by standard procedures [10], then filtered through 100 kDa cut-off filters (pore size 1.5 nm) to remove viruses. Using ultrafiltration, the SFH solution was concentrated up to 45 g Hb/dl.…”