Synthesis of Polymerized Human Serum Albumin
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Date
2011-06
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The Ohio State University
Abstract
In the event where blood for transfusion is unavailable, plasma expanders are often used to treat patients with significant blood loss. The use of many plasma expanders is often limited by their undesirable side effects. Human serum albumin (HSA) has been an attractive plasma expander. However, despite it being an important component in the blood, it can increase the risk of mortality when administered to patients with increased vascular permeability, such as in victims of severe burn injury, septic shock and endothelial dysfunction. This is caused by HSA extravasation, where HSA in the blood leaks to the surrounding tissues. This harmful side effect of HSA extravasation can be greatly reduced if the molecular size of HSA is increased. In this study, HSA was non-specifically cross-linked with glutaraldehyde. The polymerized HSA (PolyHSA) made was stabilized by a quenching reaction with NaBH4, and purified with diafiltration. The molecular weight and viscosity of the polymerized HSA increases with increasing cross-link density, and the colloid osmotic pressure (COP) decreases with increasing cross-link density. Circular dichroism shows that the secondary structure of HSA is conserved after polymerization. Altogether, these results show that glutaraldehyde can effectively cross-link HSA, significantly increase its molecular size, yielding a series of novel potential plasma expanders with high molecular weight and viscosity that prevent the harmful effects of HSA extravasation.
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Keywords
human serum albumin, glutaraldehyde, polymerization, plasma expander, hemorrhagic shock, hemodilution, anemia, transfusion