What do We Know About Albumin Formulations?

Albumin is a natural material that covers nearly 60 per cent of the human proteome and is utilised as a buffering protein that helps transport various xenobiotics in the body. Pharmaceutically, it is used for the treatment of hypovolemia in patients with chronic conditions. Albumin-based Abraxane® (paclitaxel-albumin nanoparticles) is a billion-dollar drug for treating various cancer conditions. It helped to provide an organic solvent-free formulation of a hydrophobic drug (paclitaxel). There has been an exponential rise in the research to explore various applications of albumin as a biomaterial for therapeutic and formulation development applications. As a pharmaceutical biomaterial, albumin can be moulded to form nanoparticles, hydrogels, nanofibers, and films. This article highlights key aspects, such as the synthesis and application of albumin as a pharmaceutical excipient in developing dosage forms.

1. Pharmaceutical Dosage Forms Using Albumin

Albumin is a globular protein soluble in water and coagulable by heat. It is found in egg white, blood serum, milk, and other animal and plant tissues and fluids. Human Serum Albumin (HSA) is the most abundant protein in human plasma. The use of colloidal albumin for therapeutic purposes dates back more than 50 years. Purified albumin solution is used clinically in the treatment of chronic illnesses dealing with hypovolemia (5 per cent or 25 per cent w/v). The extraction of albumin has been optimised and perfected over time. Being a natural xenobiotic career in the body, albumin (as a biomaterial) was used to synthesise nanoparticles. These are tiny particles (~200 nm size) for nanomedicine applications. HSA shows reversible binding capabilities with a range of substances, such as fatty acids, hormones, and metal ions. This makes it an ideal biomaterial for developing novel drug delivery and biomedical imaging therapeutics. This subsection narrates the uses of albumin materials in developing nanomedicines and semi-solid dosage forms.

1. 2 Nano formulations vs nanoparticles for therapeutic applications.

Albumin nanoparticles are typically prepared using various methods, including desolvation, self-assembly, thermal gelation, spray-drying, emulsification, nanoparticle albumin-bound (Nab) technology, and pH coacervation. Each of these methods has its advantages and disadvantages, and the choice of method depends on the specific requirements of the drug delivery system. The desolvation method, for example, involves the removal of solvent from a solution, causing the albumin to precipitate and form nanoparticles. On the other hand, the self-assembly method relies on the natural tendency of albumin molecules to aggregate into nanoparticles under certain physical or chemical stress conditions.

One of the most well-known commercialised albumin nanoparticles is Abraxane®, which uses a technology known as Nab technology. This technology takes advantage of the natural properties of albumin and its accumulation in tumours. The drug paclitaxel is bound to albumin and delivered to tumours without the use of toxic solvents. Abraxane® binds to the albumin receptor of the endothelial cells, activating a process called caveolae-mediated transcytosis, which enhances the delivery of the drug to the tumour. Currently,>200 clinical trials are being conducted to explore the use of Abraxane® as a single or combination therapy to develop various therapeutic options (Figure 1). Moreover, many other particles are being produced using albumin nanoparticles as a delivery system, as shown in Table 1.

Looking at the success of albumin as a nano delivery system, this biomaterial was used to develop theranostic nanomedicines for various anticancer drugs. Following are some examples:

a) Photo thermal for melanoma: A newly synthesised near-infrared dye IR-817 was combined with bovine serum albumin (BSA) to create BSA@IR-817 nanoparticles (120 to 200 nm). These nanoparticles were assessed for their fluorescence imaging (due to IR-817 dye) and photothermal (due near IR 808 irradiation) therapy potential against melanoma.

b) Photothermal therapy combined with MRI imaging of cancer: A selfassembly method of albumins with small molecules was used to encapsulate IR780 and super paramagnetic iron oxide (SPIO) nanoparticle, that forms IR780@BSA@SPIO nanoparticles. They provided NIR-II and MRI dual-mode imaging, that can accurately find cancer and guide photothermal therapy to eliminate tumours.

c) Albumin-coated or functionalised quantum dots were developed for bioimaging applications. These albuminbased nanoparticle designs were evaluated under in vitro or in vivo conditions. However, more data related to pharmacokinetics, biodistribution, dose safety and toxicity are required for their clinical testing.

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