Hemoglobin–albumin cluster: physiological responses after exchange transfusion into rats and blood circulation persistence in dogs

Abstract

A core-shell protein cluster comprising hemoglobin and human serum albumins, hemoglobin-albumin cluster (Hb-HSA 3), was designed and synthesized for use as an artificial O 2 carrier and red blood cell (RBC) substitute. For initial preclinical safety evaluation of the Hb-HSA 3 solution, we observed blood compatibility in vitro, physiological responses after exchange transfusion into rats and blood circulation lifetime in dogs. Dilution of human whole blood with Hb-HSA 3 showed an appropriate decrease in blood cell number, proportional to the mixing volume ratio. Time courses in the circulation parameters and blood gas parameters after 20% exchange transfusion with Hb-HSA 3 in anesthetized rats were almost identical to those observed in a sham group (without infusion) and an HSA group (with HSA administration) for 6 h. Serum biochemical tests of the withdrawn blood indicated safety of the protein cluster. Furthermore, fluorescent Hb-HSA 3 was infused into beagle dogs to assess blood retention. Fluorescence measurements of the blood samples enabled us to ascertain the cluster half-life within the intravascular space. Histopathologic inspections of the vital organs imply no abnormality in tissues. All these results indicate sufficient initial preclinical safety of Hb-HSA 3 as an alternative material for use in RBC transfusion.

Protein Nanoparticles: Uniting the Power of Proteins with Engineering Design Approaches

“…Preclinical studies into the safety of PNPs decorated with Pt clusters found longer half‐lives, no negative effects on vital organs, and serum biochemical markers that indicated no abnormalities when compared to the control group. [ 331 , 332 , 333 ]…”

Methemoglobin‐Albumin Cluster Incorporating Protoporphyrin IX: Dual Functional Protein Drug for Photodynamic Therapy

“…We earlier demonstrated a triangular protein cluster consisting of a Hb in the center and human serum albumins (HSAs) at the periphery (Hb‐HSA 3 ) as an artificial O 2 ‐carrier (red blood cell substitute) [14–17] . The safety and efficacy of Hb‐HSA 3 have been evaluated using animal experiments [18,19] . It is remarkable that the outside HSA moieties of Hb‐HSA 3 incorporate various hydrophobic molecules.…”

Lyophilized hemoglobin‐albumin cluster with disaccharides: Long‐term storable powder of artificial O2‐carrier

“…We earlier reported the synthesis and O 2 ‐binding property of core‐shell protein cluster consisting of a bovine hemoglobin (Hb) and human serum albumins (HSA), Hb‐HSA 3 cluster (Figure 1A). Safety and efficacy of this artificial O 2 ‐carrier solution ([Hb unit] = 5 g/dL, Figure 1B) as a red blood cell (RBC) substitute have been proven by animal experiments . However, the oxygenated Hb (oxyHb) core in the cluster is gradually oxidized to ferric metHb even at 4°C, and eventually loses the O 2 ‐transporting ability.…”