One of the body’s most abundant family of proteins could be valuable drug-delivery systems, an article in the current issue of Future Medicinal Chemistry argues. Albumin has a role in maintaining colloidal osmotic pressure in the blood; however its role as a carrier of antioxidants and waste products is of interest to the authors as it could be put to use as a chaperone for poorly water soluble drugs.
As well as improving solubility, albumin could “extend the half-life of molecules and improve drug-delivery and targeting, minimizing side effects and enhancing drug efficacy.” The enhanced targeting of albumen bound drugs is an effect of albumin concentrating in areas of inflammation and also accumulation in tumor interstitium.
An example of this drug binding is already demonstrated in the albumin-binding human insulin analog Lemevir from Novo Nordisk. One of the difficulties of insulin as a drug is being able to release it when it is needed and not cause hypoglycemia. Lemevir binds to albumin in blood and slowly dissociates, creating a pharmacodynamic profile which better fits physiological needs.
As well as treatments for diabetes, the article details albumin conjugated drugs in rheumatoid arthritis, viral infection and oncology. Aldoxorubicin, a drug currently in various clinical trials, binds albumin through an ECMH linker. Once in the acidic environment of the tumor, the linker is cleaved and the aldoxorubicin is delivered to where it is needed.
Albumin could be a solution to some of the big problems in drug development and the therapeutics on the market so far are just the beginning. The cost of late stage drug failures due to toxicity and other problems is in the billions and pharma are taking it seriously. As the authors of the article put it:
Considering that multiple drugs fail to reach the clinics due to pharmacological complications, the use of albumin as a means to improve the pharmacokinetic and pharmacodynamic properties of drug molecules, can have a major impact on their therapeutic efficacy.
Read the full article here