Brain-Penetrating Peptide Shuttles Across the Blood-Brain Barrier and Extracellular-like Space

12 June 2019, Version 1
This content is a preprint and has not undergone peer review at the time of posting.


Here, we describe a combinatorial approach to identify peptide shuttles that successfully traverse the multiple barriers to systemic drug delivery to the brain--1. the blood-brain barrier (BBB) and the 2. extracellular space (ECS) of the brain. Leveraging the excellent molecular diversity of M13 phage libraries, we identified peptides that actively transport across the BBB and diffuse through the extracellular matrix of the ECS in cell culture and in mice. These peptides demonstrate higher accumulation in the brain than gold standard peptides used in clinical trials. Importantly, these findings suggest that different sized therapeutics that were previous poorly permeable into the brain can accumulate at higher concentrations, thereby improving the therapeutic index and ultimate efficacy of drugs into the brain.


Phage Display
Blood-brain barrier
Extracellular matrix
Diffusive Transport
M13 bacteriophage
peptide shuttle


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