Current Drug Discovery Technologies - Volume 9, Issue 3, 2012

Blood substitutes, especially hemoglobin based oxygen carriers (HBOC) have been widely studied and reviewed over the past 30 years. The development of HBOCs was highlighted by crosslinking to minimize adverse effects. However, even early attempts at single crosslinking using alpha-alpha crosslinks or diaspirin crosslinking failed clinical trials due to renal morbidity and increased mortality. In fact, preclinical trials Read More

Extracellular soluble hemoglobins (Hbs) have long been studied for their possible use as safe and effective alternatives to blood transfusion. While remarkable progress has been made in the use of cell-free Hb as artificial oxygen carrier, significant problems remain, including susceptibility to oxidative inactivation and propensity to induce vasoconstriction. Hemarina-M101 is a natural giant extracellular hemoglobin (3600 kDa) Read More

To attenuate hemoglobin's (Hb) intrinsic toxicity, Texas Tech University scientists developed a novel concept of “pharmacologic cross-linking” to formulate an effective oxygen carrier, HemoTech, which consists of purified bovine Hb cross-linked intramolecularly with ATP and intermolecularly with adenosine, and conjugated with reduced glutathione (GSH). In this composition, while ATP prevents Hb dimerization, adenosine per Read More

Many researchers have tested a hemoglobin (Hb) solution as a possible oxygen carrier after discovering that one Hb molecule contains four hemes that bind and release oxygen reversibly, and that blood type antigens are expressed on the surface of red blood cells (RBCs). However, various side effects emerged during the long development of Hbbased oxygen carriers (HBOCs). The physiological significance of the RBC structure i Read More

Adverse outcomes in clinical trials on Hemoglobin Based Oxygen Carriers (HBOCs) appear to have occurred more frequently in HBOC treated than in control treated subjects. The differential may be related to many factors, including study complexity and compliance issues. Adverse outcomes also appear to be related to chronic comorbidities in subjects undergoing elective surgery. Frequently occurring comorbidities in these p Read More

Vasoconstriction is a major adverse effect of HBOCs. The use of a single drug for attenuating HBOC-induced vasoconstriction has been tried with limited success. Since HBOC causes disruptions at multiple levels of organization in the vascular system, a systems approach is helpful to explore avenues to counteract the effects of HBOC at multiple levels by targeting multiple sites in the system. A multi-target approach is especia Read More

The development of hemoglobin based oxygen therapeutics (HBOCs) requires consideration of a number of factors. While the enabling technology derives from fundamental research on protein biochemistry and biological interactions, translation of these research insights into usable medical therapeutics demands the application of considerable technical expertise and consideration and reconciliation of a myriad of manufactu Read More

Widespread clinical use of acellular hemoglobin (Hb)-based O2 carriers (HBOCs) has been hampered by their ability to elicit both vasoconstriction and systemic hypertension. This is primarily due to the ability of acellular Hb to extravasate through the blood vessel wall and scavenge endothelial-derived nitric oxide (NO). Encapsulation of Hb inside the aqueous core of liposomes retards the rates of NO dioxygenation and O2 releas Read More