Albumin as a natural and moldable biomaterial for biomimetic drug delivery applications

Natural materials such as polysaccharides, lipids, and proteins have been widely explored for their potential as nanomaterials in advanced drug delivery systems (ADDS), aiming to develop personalized biomimetic delivery platforms. Among these, albumin, the most abundant plasma protein, has garnered significant attention for its use in nanoparticle-based-drug delivery systems. This review focuses on the evolution of albumin from a key physiological biomolecule to a sustainable, green biomaterial with therapeutic and bioengineering applications. A conceptual gap still exists in understanding the dual role of albumin as a physiological matrix and as a therapeutic agent for conditions like hypovolemia, while also serving as a bulk material for ADDS development. Albumin's unique biochemical properties contribute to its role in modulating age-related diseases and maintaining physiological homeostasis. Known for its function as a physiological buffer, albumin facilitates the transport of biomolecules, drugs, and metabolites across various compartments of the human body. Clinically, albumin solutions (ranging from 5% to 25% w/v) are used in intravenous infusions to treat critically ill patients. However, albumin's structural conformation is highly sensitive to external factors such as small molecules, salts, pH variations, and temperature fluctuations, leading to aggregation and conformational changes. This negatively charged globular protein, composed of 585 amino acids and rich in cysteine (Cys), is well-suited for ionic crosslinking and composite-based pharmaceutical strategies aimed at developing novel drug delivery systems. This review bridges the existing knowledge gap by examining albumin's biochemical, clinical, and pharmaceutical characteristics, particularly its moldable chemistries for the synthesis of nanoparticles, microbubbles, hydrogels, and 3D-printable structures. Furthermore, we discuss the pharmacopeial standards and FDA regulations governing the use of albumin in clinical versus research applications. Collectively, this review highlights recent trends in research, clinical applications, and the potential of albumin as a pharmaceutical excipient for developing personalized site-directed dosage formulations.