The therapeutic efficacy of any drug depends on how effectively it can be delivered to the target site. This is where drug delivery mechanisms and carriers play a critical role to ensure proficient pharmacodynamics and pharmacokinetics. The availability of the drug at the target site, at the right time and right concentration helps to enhance its therapeutic performance and reduce any unwanted side-effects.
Drug carriers are crucial as therapeutic drugs are low molecular weight that can often result in non-specific dispersal, renal clearance, or short term availability in the plasma without supporting carriers. This is where drug delivery technology comes in picture to overcome the challenges of low therapeutic efficiency of drugs.
Albumin: Self drug delivery
To date PEGylation (using polyethylene glycol) is a commonly used method for drug delivery. Though it has proven to highly effective for a multitude of drugs in the market, it does have some drawbacks. This majorly includes the accumulation of polyethylene glycol in body tissues such as the liver. Moreover, the method also requires chemical conjugation of the drug for increasing the drug delivery efficiency which often raises multiple concerns. In light of these challenges, albumin-based drug delivery technology offers a proficient solution in the coming times.
Albumin is the next big thing in drug delivery technology due to its unique properties. Being abundantly available in blood plasma, albumin is known as the natural drug carrier. It helps in the transport of various nutrients and biological components to the different parts of the body which can be exploited to commercialize it as a potential drug delivery agent. Albumin has multiple binding sites and a great half-life of up to 19 days which proves to be crucial to harnessing it as a drug carrier. Though there are some challenges with plasma-derived albumin, it’s alternative recombinant human serum albumin can prove to be a highly successful drug delivery agent due to its properties of being animal origin free, endotoxin free and high purity.
Recombinant albumin can effectively interact with multiple cellular receptors that facilitate its transport across the tissues. Some of these key receptors include Gp60, Gp30, Gp18, SPARC (Secreted Protein Acidic and Rich in Cysteine), and the FcRn receptor (also known as neonatal Fc receptor). Understanding the interaction of albumin with these receptors can help unfold the underlying mechanism of drug cargo delivery across tissues. Among these receptors glycoprotein receptor, i.e. Gp60 also known as albodin plays a vital role in increasing membrane permeability to support receptor-mediated transport of the proteins. Drug carriers like albumin having specificity for Gp60 receptor when binds, it activates the caveolin-1 (membrane protein) inducing the formation of vesicle which later merges with basolateral membrane and transports the cargo from its pouch. Thus, Gp60 binding helps albumin for cellular transcytosis and overcome the lysosomal degradation which occurs otherwise.
In order to increase the efficacy of drug delivery, one can incorporate bio-components that mimic as ligands for albumin such as fatty acids. This has been commonly used by various companies, for example, Levemir and Victoza of Novo Nordisk contain myristic acid and palmitic acid respectively. These drugs are widely used for the treatment of diabetes. Upon injecting them, the acidic group binds to albumin and gets distributed to the target site by the mechanism mentioned earlier. Thus, enhancing the overall bioavailability of the drug. Another example is Celgene’s Abraxane which is a nanoparticle albumin-bound paclitaxel complex, widely used for the treatment of metastatic breast cancer.
The use of recombinant albumin for increasing the half-life or target drug delivery is growing day by day due to its invincible properties. This is very much evident from the number of products available in the market which are dependent on recombinant albumin mediated drug delivery. The sales figure for these products is known to be on the rise. Moreover, the great amount of pipeline applications of recombinant albumin which are presently in clinical trials is prompting biopharmaceutical manufacturers to make a shift towards recombinant albumin research and development. In the coming times, it can be predicted that recombinant albumin will be one of the key components as an agent for setting in enhanced drug delivery paradigm. Let’s see how the market and companies identify the potential and set it into action.
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Maja Thim Larsen et.al, Albumin-based drug delivery: harnessing nature to cure disease, Molecular and Cellular Therapies volume 4, Article number: 3 (2016)