Molecular Peptide Vectors Emerging Paradigm For Blood-brain Barrier Delivery

A new class of drug transporters have the capacity to reach the brain more efficiently, fusing chemistry, pharmacy and biomedicine, say researchers.

IRB Barcelona scientists Benjamí Oller, Macarena Sánchez, Ernest Giralt, and Meritxell Teixidó, all from the Peptides and Proteins Lab of the Chemistry and Molecular Pharmacology Program, have authored a review on the emerging field of shuttle peptides, molecules that have the capacity to transport drugs across the blood-brain barrier and thus treat diseases affecting the central nervous system.

Ten years ago, IRB Barcelona group leader Ernest Giralt started work on peptide shuttles to overcome the blood-brain barrier — a line of research that Dr. Meritxell Teixidó is now in charge of.

This is one of the few expert groups worldwide in the field, having published 15 scientific articles and holding 4 patents.

Molecular Peptide Vectors

The authors point out that the administration of drugs to the brain is one of the main challenges of drug development, given the significant number of patients with neurological diseases and the low efficiency of the treatments currently available. Although the barrier that protects the brain, known as the blood-brain barrier (BBB), limits the capacity of drugs, many with great potential, to reach their target, molecular peptide vectors, known as BBB shuttles, are emerging as a promising tool to overcome this obstacle.

In recent years, transporters based on small proteins known as peptides are attracting attention in the field due to their low production cost, small effect on immune system response, and chemical versatility compared with traditional antibodies and other larger proteins.

The review article presents the blood-brain barrier as a formidable obstacle but at the same time a great opportunity for the administration of drugs to the brain. The review provides an introduction to the concept of peptide shuttles and makes reference to the most important ones, paying special mention to two peptides that have reached clinical assays.

It then goes on to explain three examples of shuttles that highlight the main advances in relation to several types of cargo that they can transport, and some basic features to be viable as drugs, such as protease-resistance, which allows long life in blood. The researchers finally describe current trends and challenges to tackle to achieve the next generation of shuttle peptides.

Benjamí Oller-Salvia, Macarena Sánchez-Navarro, Ernest Giralt, Meritxell Teixidó
Blood–brain barrier shuttle peptides: an emerging paradigm for brain delivery
Chem. Soc. Rev., 2016; 45 (17): 4690 DOI: 10.1039/C6CS00076B