Stability of albumin and stabilization of albumin preparations

Abstract

Human serum albumin (HSA) is structurally stabilized by 17 disulfide bonds, and interactions between domains (or subdomains) of HSA also contribute to its stability. The effects of several other factors on the stability of HSA and pharmaceutical preparations that contain HSA have been widely investigated. When HSA is heated and in the presence of chemical denaturants, unfolding occurs through multiple steps, and the genetic variations of HSA and ligand binding to HSA have been shown to contribute to protecting HSA against such irreversible structural changes. HSA is therapeutically used for treating shock, burns, hypoalbuminemia, surgery, trauma, cardiopulmonary bypass, acute respiratory distress, or hemodialysis, and its pharmaceutical preparations are supplied in the form of sterilized aqueous solutions. These solutions contain sodium octanoate and N-acetyl-l-tryptophanate to prevent the irreversible denaturation of HSA that occurs during pasteurization by heating at 60 °C for 10 h. Sodium octanoate has the greatest stabilizing effect against heat, whereas the presence of N-acetyl-l-tryptophanate diminishes the oxidation of HSA. Recently, N-acetyl-methioninate, as a new stabilizer, has been suggested to be superior to N-acetyl-l-tryptophanate with respect to scavenging reactive oxygen species and in protecting the protein against oxidation. Nanoparticle and fusion proteins which contain HSA as a carrier for drug delivery are being actively developed. In addition to the use of sodium octanoate and N-acetyl-l-tryptophanate as a stabilizer for nanoparticles of paclitaxel, to stabilize HSA fusion proteins, ligand binding to HSA domains, genetic mutations of HSA domains, and lyophilization using sugars or surfactants are used.