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chemRxiv_Peng.pdf (1.54 MB)
Brain-Penetrating Peptide Shuttles Across the Blood-Brain Barrier and Extracellular-like Space
Preprints are manuscripts made publicly available before they have been submitted for formal peer review and publication. They might contain new research findings or data. Preprints can be a draft or final version of an author's research but must not have been accepted for publication at the time of submission.
submitted on 07.06.2019 and posted on 12.06.2019by Xiujuan Peng, Xinquan Liu, Yen-Liang Liu, Jae You Kim, Yuan-I Chen, Phyllis Ang, Alex Nguyen, Jasmim Leal, Hsin-Chih Yeh, Debadyuti Ghosh
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.