PEGylation of Apohemoglobin Haptoglobin Complex reduces Associated Free Stroma Hemoglobin Toxicities

Apohemglobin (ApoHb) haptoglobin (Hp) complex (ApoHb-Hp) is a hemoglobin (Hb) and heme scavenging protein that leverages Hp acellular free Hb scavenging capacity and apoHb free circulating heme scavenging capacity. This protein complex provides substantial relief against hemolytic anemia such as sickle cell, thalassemia, and IMHA (immune-mediated hemolytic anemia). Unfortunately, apoHb is highly unstable at physiological temperature, forming protein aggregates and precipitates. These characteristics diminish the potential benefits of using the heme scavenger in vivo. To address the issues associated with ApoHb, the protein was conjugated with polyethylene glycol (PEG). By modifying the surface of apoHb, the protein increases in size and increases its circulatory half-life. However, its effectiveness does decrease as the surface modification sterically hinders active sites.The aim of the present study was to evaluate the i n vivo effects of PEG-apoHb-Hp complex by challenging it against a bolus injection (10% of the animal’s blood volume) of human Hb utilizing intravital microscopy on male Golden Syrian hamsters instrumented with dorsal window chamber. This study evaluated four experimental treatment groups saline, PEG-apoHb only, Hp only, and PEG-apoHb-Hp under the hHb challenge. The microvascular hemodynamics (flow) in arterioles < 50 μm, arterioles > 50 μm and venules 20更多