Hemoglobin-Vesicles as a Transfusion Alternative

Abstract

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.

Blood Substitutes

“…In these studies, several LEH preparations improved systemic O 2 -transport [112] and cerebral tissue oxygenation [111,122] after fluid resuscitation. Of note, LEH do not have any oncotic effect, so the treatment modality of LEH in shock is similar to that of PFC, i.e., supplementation of colloidal fluid replacement with oxygen carrying liposomes.…”

Novel strategies for transporting cellular hemoglobin‐based oxygen carriers in the systemic circulation

“…Recently (2006), Tsuchida's group suspended PEGylated HbVs in a 5 g/dL recombinant human serum albumin (rHSA) solution (HbV/rHSA) 23 . For controls, they prepared washed homologous RBCs (8.6 g/dL of Hb) suspended in rHSA solution (wRBC/rHSA), shed autologous blood (SAB), and rHSA alone.…”

“…Radioisotope‐labeled HbVs were monitored to measure t 1/2 . At a dose of 14 mL/kg, the t 1/2 was 32 hours in rats (circulatory half‐life depended on dose‐rate) 12,22,23 …”

Nanobiotechnology-based Blood Substitutes and the Cardiovascular Systems in Transfusion Medicine

“…Extensive research has been carried out by many groups using lipid membrane to encapsulate Hb into 200 nm lipid-encapsulated Hb (LEH) (Djordjevich and Miller 1980;Phillips et al 1999;Tsuchida et al 2006). The use of PEG-lipid membrane to form 200 nm diameter PEG-lipid membrane artifi cial rbc increased the circulation time to a clinically useful level (Phillips et al 1999).…”