Y. Ogata et al., CHARACTERISTICS OF NEO-RED-CELLS, THEIR FUNCTION AND SAFETY - IN-VIVOSTUDIES, Artificial cells, blood substitutes, and immobilization biotechnology, 22(3), 1994, pp. 875-881
A new type of artificial oxygen carriers, the Neo Red Cells (NRCs) hav
e been developed and investigated for oxygen transporting efficiency a
nd safety in experimental animals. Stroma free hemoglobin from outdate
d human red blood cells together with inositol hexaphosphate as an all
osteric effector under sterile, pyrogen free condition were encapsulat
ed in liposomes and then were coated with polyethylene glycol bond to
hydrogenated soy phosphatidylethanolamine as a surface modifier to pre
vent aggregation of NRCs in plasma. The efficiency of the NRCs in tiss
ue oxygenation was studied in rabbits which were made severely anemic
by drawing 85% of their blood and immediately replacing it with NRC so
lution. The animals, all recovered to pre-anemic conditions within 6-8
hr and lived normally until being sacrificed, 6 months after the exch
ange transfusion. The circulation half-life and tissue distribution of
NRCs were studied using radiolabeled NRCs. Within the circulation, th
e half-life of NRCs was 21 hr and extravascularly, they were distribut
ed mainly in and metabolized by the reticuloendothelial system within
7 days. Our observations suggest that the NRCs prepared and investigat
ed in this study are efficient oxygen carriers without causing serious
adverse reactions and can be prepared free from pathogenic micro-orga
nisms by special filtration technique before encapsulation of Hb. Curr
ently, experiments are ongoing to control auto-oxidation of oxyHb to m
etHb which is higher in NRCs than in native red cells at physiological
conditions.