Recombinant Human Albumin Liquid For Drug Delivery rHSA Recombinant Human Protein

Recombinant human albumin liquid for drug delivery

Human serum albumin (HSA) exhibits an average half-life of 19 days. The functions and binding properties of HSA are multifold: a) it acts as the solubilizing agent for long chain fatty acids and is therefore essential for the metabolism of lipids; b) it binds bilirubin, the breakdown product of heme; c) it binds a great number of therapeutic drugs such as penicillins, sulfonamides; d) it binds copper(II) and nickel(II) in a specific and calcium(II) and zinc(II) in a relatively nonspecific manner and acts as the transport vehicle for these metal ions in the blood; e) it is the major protein responsible for the colloid osmotic pressure of the blood; f) when HSA is broken down, the amino acids provide nutrition to peripheral tissue.

HSA is known to act as a carrier protein, mainly through two docking sites for drugs and 7–9 sites for fatty acids. Eight myristic acids were observed bound to the recombinant human albumin molecule, and all fatty acid binding sites in recombinant humen albumin (OsrHSA) were identified at the same locations as in plasma HAS (pHSA) (Fig. D). Two drug binding sites found in pHSA were also present in OsrHSA. Site I is a hydrophobic cavity located in subdomain II. Two clusters of polar residues responsible for ligand interaction were populated by amino acids Y150, H242, R257, and K195, K199, R218, R222, respectively (Fig. E). Site II was another hydrophobic pocket in subdomain IIIA composed of L387, Y411, L453, V433, and L430. One polar region, made up of R410, K414, and S489, was found in this binding site (Fig. F). The structural topology of these binding sites in OsrHSA suggests that it can perform the same biological functions as pHSA.

One of the most important biological activities of HSA is its binding capacity for various ligands; thus, two site-specific drug markers, warfarin (site I) and naproxen (site II), were used to evaluate the binding capacity of OsrHSA. The binding assay showed that the affinities of warfarin and naproxen to OsrHSA is similar to the binding affinities observed to pHSA, indicating that no significant difference in drug-binding affinity exists between OsrHSA and pHSA.

Recombinant human albumin (OsrHSA) is an acidic, very soluble protein that is extremely robust: it is stable in the pH range of 4–9, soluble in 40% ethanol, and can be heated at 60 °C for up to 10 h without deleterious effects. These properties as well as its preferential uptake in tumor and inflamed tissue, its ready availability, its biodegradability, and its lack of toxicity and immunogenicity make it an ideal candidate for drug delivery.