Human serum albumin (HSA) is a vital protein synthesised in the human liver and secreted into the bloodstream. Constituting approximately 50% of the total plasma proteins, HSA plays a pivotal role in various physiological processes.

What is Human Serum Albumin & how does it look?

HSA is a water-soluble monomeric macromolecule with a molecular weight of 66.5 kDa and consists of 585 amino acid residues. Structurally, HSA consists of one N-terminus, one C-terminus, and three homologous domains, each comprising two helical subdomains. Remarkably, HSA features several binding pockets capable of accommodating diverse ligands, including fatty acids and ions, offering non-covalent binding sites for drugs.

This versatile protein has a compact heart-shaped structure held together by 17 internal disulfide bridges. Additionally, HSA possesses a free amino acid cysteine at position 34 (Cys34) situated on the surface of the albumin molecule.

HSA serves as a carrier protein, facilitating the transport of hormones and fatty acids, and playing a crucial role in pH buffering. It also plays a pivotal role in stabilising extracellular fluid volume and maintaining oncotic pressure.

Notably, HSA exhibits remarkable stability within the bloodstream, with a half-life of approximately 19 days. This longevity enables it to efficiently traverse in and out of blood vessels. Given these attributes, HSA stands out as an excellent carrier for various ligands, making it a promising candidate for drug delivery applications.

The utility of HSA extends beyond its physiological functions. It has wide-ranging applications in pharmaceutical, diagnostic, therapeutic, and biotechnological, as described below:

1. Human Serum Albumin as Drug Delivery Vehicles

Nanomedicine has shown great potential in pharmaceutical applications. Numerous nanoparticles have been designed to fulfil a range of critical functions, from efficient drug administration to safeguarding and delivering therapeutics that pose significant challenges. Among these, albumin has garnered substantial attention, emerging as an exceptionally enticing carrier for drug delivery, and for a multitude of compelling reasons.

Firstly, albumin is the most abundant protein in the plasma and emerges as a natural choice for drug delivery. This supremacy in abundance is coupled with an inherent compatibility with the human body, showcasing high levels of biocompatibility, biodegradability, and a commendable non-immunogenic profile. These attributes collectively render albumin a well-suited candidate for orchestrating the complex symphony of drug delivery.

Secondly, albumin has an extended half-life, amplifying its utility as a drug delivery vehicle. Beyond its temporal persistence, the structural and conformational features of albumin open doors to versatile interactions with a wide array of therapeutic agents. This multifaceted capability aids in the stabilisation and protection of drugs, shielding them from premature elimination and metabolic degradation. Such protective actions invariably enhance the pharmacokinetic properties of the administered drugs, promising improved effectiveness.

Secondly, albumin has an extended half-life, amplifying its utility as a drug delivery vehicle. Beyond its temporal persistence, the structural and conformational features of albumin open doors to versatile interactions with a wide array of therapeutic agents. This multifaceted capability aids in the stabilisation and protection of drugs, shielding them from premature elimination and metabolic degradation. Such protective actions invariably enhance the pharmacokinetic properties of the administered drugs, promising improved effectiveness.

The uniqueness of albumin lies in its capacity to facilitate both passive and active drug targeting. While its inherent properties allow it to serve as an effective carrier for pharmaceutical agents through passive mechanisms, its adaptability, and versatility extend the boundaries of drug delivery through active targeting strategies, elevating the prospects of tailored therapeutic interventions.

2. Human Serum Albumin Use in Stem Cell Therapy

Stem cell therapy has emerged as a transformative approach across diverse clinical domains, offering hope for treating an extensive array of conditions, including spinal cord injuries, heart disease, liver disease, cancer, burns, and osteoarthritis. Amidst the manifold intricacies involved in stem cell therapies, the paramount goal is to ensure the stability and reliability of the final stem cell product, a critical factor influencing both efficacy and safety. To achieve this, it becomes imperative to comprehensively comprehend and meticulously control the entire workflow, spanning from cell harvesting and culture to preservation and therapeutic administration, thereby optimising the vitality and consistency of these remarkable cells.

Albumin has etched a longstanding presence as an indispensable component of cell culture media. Its well-documented ability to foster the growth of diverse cell types, including mesenchymal stem cells (MSCs), embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), and immune cells, is a testament to its multifaceted utility. In the context of cell culture, albumin serves as far more than a nutritional source. It assumes the role of a versatile reservoir, safeguarding essential metals and other molecular entities, thereby creating an optimal milieu for sustained cell growth and viability. Furthermore, albumin functions as a pH buffer, stabilising the cellular environment, and stands as a formidable shield against toxins and reactive oxygen radicals, shielding delicate cells from stress-induced harm.

Beyond its contributions to cell culture, albumin’s utility extends to stem cell cryopreservation. Here, albumin’s unique attributes prove invaluable. Its exceptional ability to coat surfaces ensures the safekeeping of cells during the freezing process. Additionally, albumin’s remarkable buffering capacity preserves the pH balance essential for cellular integrity, while its stabilising prowess maintains cells in a suspended state, extending their viability window during cryopreservation. This property is particularly vital in stem cell therapies, where the controlled preservation of cells until their therapeutic use is crucial.

Albumin plays a foundational role in stem cell therapies. Its versatility as a growth facilitator, protector, and cryopreservation champion underscores its significance in the pursuit of harnessing the full potential of stem cells for transformative healthcare solutions. As research advances, albumin’s contributions are likely to further elevate the precision and effectiveness of stem cell therapies, offering renewed hope to patients and practitioners alike.

3. Human Serum Albumin for Diagnostic and Therapeutic Application

HSA emerges as a versatile and invaluable biomarker across a spectrum of diseases, encompassing conditions like cancer, rheumatoid arthritis, ischemia, liver disease, obesity, and diabetes. Notably, in patients grappling with chronic liver disease, the plasma HSA undergoes a profound change in conformation owing to the pathologically elevated levels of fatty acids and bilirubin. This altered conformation may accelerate irreversible post-translational modifications, thereby diminishing the functional albumin concentration. This intricate interplay between HSA and disease-associated changes underscores its significance as a diagnostic indicator.

In clinical applications, HSA is used in the treatment of several pathologies, including shock, trauma, haemorrhage, acute respiratory distress syndrome, hemodialysis, liver disease, and hypoalbuminemia. The normal serum concentration of albumin in healthy adults hovers between approximately 35 to 50 g/L. However, a decline in circulating albumin levels, a condition known as hypoalbuminemia, frequently afflicts seriously ill patients. This phenomenon is especially prevalent among hospitalised individuals and often aligns with various diseases such as cirrhosis, malnutrition, nephrotic syndrome, and sepsis. The management of hypoalbuminemia often involves albumin infusions, a therapeutic measure that underscores the remarkable versatility of HSA as a clinical tool.

In summary, HSA’s dual role as a diagnostic biomarker and a therapeutic agent mirrors its adaptability and significance in the ever-evolving landscape of healthcare. Its unique ability to reflect disease-related alterations and to serve as a treatment modality positions HSA as a pivotal contributor to the quest for precision medicine and enhanced patient care.

4. Human Serum Albumin Use in Vaccine Manufacturing

HSA stands as a vital ingredient in the stabilisation of vaccines, offering its versatile benefits to a wide spectrum of vaccine types, including live attenuated viruses, inactivated or killed viruses, virus-like particles, and subunit vaccines.

One of HSA’s remarkable attributes lies in its ability to coat both hydrophobic and hydrophilic surfaces, thereby thwarting the undesirable nonspecific adsorption of vaccines throughout the entire lifecycle, from production and formulation to storage. By enveloping these surfaces, HSA acts as a sentinel, preventing surface-induced unfolding and aggregation events of the crucial active pharmaceutical ingredients (APIs). Through its binding prowess, capable of both ionic and hydrophobic interactions, HSA safeguards the exposed vaccine surfaces, averting unwanted aggregation and particle formation, which could otherwise compromise vaccine efficacy.

HSA’s significance extends to its formidable anti-oxidation capabilities, serving as a guardian for APIs against oxidative modifications. This protective prowess is attributed to a free thiol group, specifically cysteine 34 within HSA. This unpaired cysteine residue, in its reduced form, proves more susceptible to oxidation than the APIs under conditions of oxidative stress. By sacrificially absorbing oxidative insults, HSA shields the vaccine’s active components from undergoing undesirable alterations, thereby preserving their efficacy and safety.

Several vaccines have harnessed the stabilising influence of HSA as an excipient. Some examples are MMR® II, vaccine against measles, mumps, and rubella, and Varilrix™, vaccine against chickenpox. By incorporating HSA into its formulation, these vaccines capitalise on the unique properties of HSA to ensure the potency, stability, and safety of the vaccine product, ultimately contributing to the effectiveness of immunisation efforts.

The multifaceted characteristics of HSA present a wide array of possibilities for various innovations, spanning from enhancing pharmaceutical drug delivery to supporting therapeutic and diagnostic assays, as well as finding applications in biotechnology. As ongoing research continues to evolve, Human and Clinical Grade HSA stands ready to play a pivotal role in driving progress across healthcare, biotechnology, and other sectors, ultimately fostering improvements in human health and overall well-being.

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References

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