Albumin, a major blood protein made by the liver, may soon become the vehicle to deliver drugs to specific targets within the body, said Eva Frei of the German Cancer Research Center (DKFZ) at Heidelberg in Germany. Eva was in the state to give a lecture at the ongoing international seminar on ‘Recent biochemical approaches in therapeutics’ organised by Kerala University’s Department of Biochemistry at Thiruvananthapuram.
"Albumin is the chief circulating protein in the blood and is a transport protein for many compounds. Albumin is becoming increasingly important as a drug carrier in cancer therapy since numerous preclinical studies have demonstrated an accumulation of albumin in inflammations as well as solid tumours,’’ she said. This accumulation of albumin in solid tumours formed the basis for developing albumin-based drug delivery systems.
The work on the possibility of using albumin as a drug carrier started almost a decade ago. ‘’The amount of drug that can be carried through the albumin is very little. If you load it with too much drugs, the body will not recognise albumin and an immune response will be initiated. Once the antibodies are formed within the body, then that is the end. You won’t be able to use it again as the antibodies will be active,’’ said Eva.
When the load is heavy, the drug is ineffective in animal studies even while showing promise in the in vitro studies. ‘’Some of the earlier studies, for example that of methotrixate, ran into difficulties in the clinical trial stage as the drug carried by the albumin was too less to be effective. Alternatively, we should have used a more potent drug. But still, the idea is being improved upon,’’ said Eva, who likes to call the drug combined albumin conjugates as magic bullets.
Some of the drugs developed by the albumin-based drug delivery technology are in advancing phases of clinical trials and several promising products are in the pipeline.
Albuferon, a fusion protein of albumin and interferon, is currently being assessed in phase III clinical trials for the treatment of Hepatitis C.
"This albumin-based approach has been applied to several peptides for antiviral activity, against diabetes and anti-tumour. Levemir, a myristic acid derivative of insulin that binds to albumin, was approved long ago. In fact, binding albumin with doxorubicin, that was tried even before the methotrixate, was very promising,’’ said Eva.
Problems, Eva said, could arise at the dissociation of drug from the carrier. Right from the start, scientists would need to design an enzymatically cleavable bond between the drug and the carrier to make it available in the body. The biggest problem however, Eva said, is with conducting the clinical trials.
"It is so very expensive. A collaboration with the pharmaceutical industry is absolutely essential. And as the patent gets older, the revenue for the pharmaceutical company decreases and they lose interest. Drug development in Germany cannot happen without funds from the pharma companies,’’ said Eva, who is on her first trip to Kerala.
However, this albumin-approach is now being tried out in the development of diagnostic tools as well. "Albumin can be tagged with aminofluorescein stain. This type of staining of brain tumours can help in brain surgery,’’ said Eva.
"Of course, this is not a cure and only time will tell as to how effective this will be,’’ she concluded.