Red Blood Cells as Drug Shuttles

redbloodcell

Illustration of red blood cells. Source: pixabay.com

The discovery and development of a new drug is an enormously costly task. Analysis last year estimated that large pharmaceutical companies can expect to spend $5 billion to take a molecule through from discovery to being an approved new medicine on the market. This immense cost is in part due to the failure rate associated with drug discovery. Of every 5,000 to 10,000 compounds that enter the research and development (R&D) process, only one will receive approval.

Molecules can be withdrawn from various stages of this process for a number of reasons. These can include safety, lack of efficacy or a poor pharmacokinetic profile. Pharmacokinetics describe the movement of a drug into, through, and out of the body – namely the absorption, distribution, metabolism and excretion of the drug.

In order to challenge the unsustainable costs and failure rates seen in drug discovery, several groups of scientists are exploring alternative methods of drug delivery to try to recover otherwise discarded molecules. Compounds which show significant activity in vitro often fail to reproduce this effect in vivo due to rapid metabolism in the body which can lead to inactive or even toxic derivatives. Further investigation into such compounds is often then abandoned. New research seeks to explore novel approaches to delivering unmetabolised intact drug molecules to the required site in the body.

Researchers at the Whitehead Institute for Biomedical Research in Massachusetts have been examining the possibility of exploiting red blood cells (RBCs) as intravenous carriers for drug delivery. RBCs circulate the body for around 120 days, and constitute a quarter of all the cells in the body. These cells therefore present an attractive potential carrier of therapeutics or biological probes. The team isolated RBC precursors from bone marrow samples and then generated normal RBCs in tissue culture. They then introduced a gene to the cells encoding surface proteins that can be covalently modified at site-specific locations. In this way surface proteins act as a tether to attach a vast array of molecules to the RBCs. The modification process was found not to damage cells or affect their survival in vivo.

This work presents an insight into an emerging area of drug development, hopefully one that will continue to be explored so that one day failure rates might not pose such a threat to the invention of new medicines.

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Bethany Small

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