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Synthesis and biophysical properties of polymerized human serum albumin
Author(s) -
Elmer Jacob,
Cabrales Pedro,
Wang Qi,
Zhang Ning,
Palmer Andre F.
Publication year - 2011
Publication title -
biotechnology progress
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.572
H-Index - 129
eISSN - 1520-6033
pISSN - 8756-7938
DOI - 10.1002/btpr.531
Subject(s) - hydroxyethyl starch , human serum albumin , glutaraldehyde , chemistry , extravasation , polymerization , dextran , albumin , serum albumin , oncotic pressure , osmotic pressure , polymer chemistry , biophysics , polymer , biochemistry , chromatography , organic chemistry , immunology , medicine , biology
The use of many plasma expanders (PEs) is often limited by undesirable side effects, such as red blood cell (RBC) aggregation (hydroxyethyl starch), nephrotoxicity (dextran), and extravasation (albumin). Despite its natural prevalence in the bloodstream, human serum albumin (HSA) can increase the risk of mortality when administered to patients with increased vascular permeability (i.e., patients suffering from burns, septic shock, and endothelial dysfunction). The harmful extravasation of HSA can be limited by polymerizing HSA to increase its molecular size. In this study, HSA was nonspecifically cross‐linked with glutaraldehyde at different cross‐link densities by varying the molar ratio of glutaraldehyde to HSA. The results of this study show that the weight‐averaged molecular weight (MW), viscosity, and extent of RBC aggregation of polymerized HSA increases with increasing cross‐link density, whereas the colloid osmotic pressure (COP) decreases with increasing cross‐link density. Interestingly, circular dichroism measurements indicate that the secondary structure of HSA is unaffected by polymerization. Altogether, these results show that glutaraldehyde can effectively cross‐link HSA to produce high MW polymers, yielding a novel series of potential PEs that exhibit low COP and high viscosity. © 2011 American Institute of Chemical Engineers Biotechnol. Prog., 2011