Clinical Snapshot: Albumin

Albumin is the most abundant protein in human plasma, making up about half of the total serum protein. It is synthesized by the liver at a rate of 10 to 15 grams per day and has a molecular weight of 66.5 kDa.1,2,8

With a circulating half-life of 19 to 21 days, albumin is a stable and highly soluble protein.11

It plays a central role in maintaining plasma oncotic pressure and serves as a versatile carrier for a wide range of endogenous molecules such as bilirubin, fatty acids, hormones, and metals, as well as exogenous drugs.8,17

Its heart-shaped structure and multiple binding sites make it uniquely suited to these functions.11

Key Physiologic Roles

Roles

Transport: carries hormones, fatty acids, bilirubin, metals, and many small molecules including drugs 9

Homeostasis: maintains fluid balance across capillary membranes, buffers pH, and helps regulate amino acid supply 18

Binding capacity: interacts with a wide range of hydrophobic ligands, influencing pharmacokinetics, and contributes to antioxidant defense18

Albumin provides about 70 percent of plasma oncotic pressure, which is critical for maintaining fluid balance across capillary membranes.9

It also serves as a transport protein, carrying bilirubin, fatty acids, hormones, metals, and many exogenous drugs.8

Albumin’s free thiol group at cysteine-34 gives it antioxidant properties, helping to neutralize oxidative stress.14

Albumin as a Carrier

Albumin’s long half-life, stability, and ability to accumulate in tissues with increased vascular permeability make it an ideal carrier system for therapeutics.11

In oncology, albumin has been harnessed to deliver chemotherapies and biologics directly to tumors through the enhanced permeability and retention effect.13

In immunology, albumin has been engineered to enhance the pharmacokinetics of immunomodulators such as recombinant interleukin-2 and to improve vaccine delivery efficiency through albumin-binding platforms.1

In diagnostics, albumin-binding contrast agents have been developed to enhance imaging resolution.10

Albumin in Oncology and Chemotherapy

Albumin has also been developed as a carrier and excipient to improve the formulation and delivery of hydrophobic cytotoxic agents. By binding to albumin, these drugs can be more effectively transported in plasma and delivered to tumor sites.¹³

Several transport pathways have been proposed. These include endothelial transcytosis mediated by receptors such as gp60, as well as interactions with extracellular matrix proteins like SPARC (secreted protein acidic and rich in cysteine), which may facilitate tumor accumulation.³

Quick Facts

Abundant plasma protein: makes up about half of total plasma protein, with a molecular weight of ~66 kDa.2,8,13

Long half-life: remains in circulation for 2–3 weeks due to FcRn recycling, giving albumin stability and extended availability.11

Oncotic pressure: provides around 70% of plasma colloid osmotic pressure, maintaining fluid balance across capillary membranes.9

Transport and binding: carries bilirubin, fatty acids, hormones, metals, and many drugs; its binding to hydrophobic ligands influences pharmacokinetics.9,10

Protective roles: contributes to antioxidant defense through Cys34, buffers pH, and serves as a circulating amino acid reservoir. 14,18

References

  1. Hoogenboezem, E. N., & Duvall, C. L. (2018). Harnessing albumin as a carrier for cancer therapies. Advanced Drug Delivery Reviews, 130, 73–89.

  2. Larsen, M. T., Kuhlmann, M., Hvam, M. L., & Howard, K. A. (2016). Albumin-based drug delivery: Harnessing nature to cure disease. Molecular and Cellular Therapies, 4(1), Article 3.

  3. Merlot, A. M., Kalinowski, D. S., & Richardson, D. R. (2014). Unraveling the mysteries of serum albumin — more than just a serum protein. Frontiers in Physiology, 5, 299.

  4. Human Albumin; in Cross-Sectional Guidelines for Therapy with Blood Components and Plasma Derivatives, 4th ed. Transfus Med Hemother 2009; 36(6):399-407 Albert Farrugia.

  5. U.S. Food and Drug Administration. Albumin (Human) 5%—Prescribing Information. Silver Spring, MD: FDA; 2006. Available from: https://www.fda.gov/media/113696/download. 

  6. Steel, L. F., Trotter, M. G., Nakajima, P. B., Mattu, T. S., Gonye, G., & Block, T. (2003). Efficient and specific removal of albumin from human serum samples. Molecular & Cellular Proteomics, 2(4), 262-270.

  7. Louten, J. (2016). Virus structure and classification. In Essential Human Virology (pp. 37-65). Academic Press.

  8. Moman RN, Gupta N, Varacallo MA. Physiology, Albumin. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Dec 26.

  9. Busher JT. Serum Albumin and Globulin. In: Walker HK, Hall WD, Hurst JW, editors. Clinical Methods: The History, Physical, and Laboratory Examinations. 3rd ed. Boston: Butterworths; 1990.

  10. Zorzi A, Linciano S, Angelini A. Non-covalent albumin-binding ligands for extending the circulating half-life of small biotherapeutics. MedChemComm. 2019;10(7):1068–81.

  11. Sand KMK, Bern M, Nilsen J, Noordzij HT, Sandlie I, Andersen JT. Unraveling the interaction between FcRn and albumin: opportunities for design of albumin-based therapeutics. Front Immunol. 2015;5:682.

  12. Erickson HP. Size and shape of protein molecules at the nanometer level determined by sedimentation, gel filtration, and electron microscopy. Biol Proced Online. 2009;11:32–51.

  13. Hoogenboezem EN, Duvall CL. Harnessing albumin as a carrier for cancer therapies. Adv Drug Deliv Rev. 2019;144:138–52.

  14. Tabata, F.; Wada Y.; Kawakami, S.; Miyaji, K. Serum Albumin Redox States: More than Oxidative Stress Biomarker. Antioxidants 2021, 10, 503.

  15. Fanali G, di Masi A, Trezza V, Marino M, Fasano M, Ascenzi P. Human serum albumin: From bench to bedside. Mol Aspects Med. 2012;33(3):209-290.

  16. 5 Human Albumin. Transfus Med Hemother. 2009;36(6):399-407. PMID: 21245971; PMCID: PMC2997295. https://pmc.ncbi.nlm.nih.gov/articles/PMC2997295/

  17. Chien SC, Chen CY, Lin CF, Yeh HI. Critical appraisal of the role of serum albumin in cardiovascular disease. Biomark Res. 2017;5:31.

  18. Hutapea, T. P. H., Madurani, K. A., Syahputra, M. Y., Hudha, M. N., Asriana, A. N., Suprapto, & Kurniawan, F. (2023). Albumin: Source, preparation, determination, applications, and prospects. Journal of Science: Advanced Materials and Devices, 8(2), 100549.