Investigation of Nose-to-Brain Transportation of Peptide-Displaying Bacteriophage Particles Using Phage Display Method

Abstract

Background: Brain drug delivery is of paramount significance in CNS-related diseases as blood brain barrier (BBB) permeability is not feasible for many pharmaceutical agents. The purpose of this study was to investigate the identification of peptide sequences with specific translocation into brain via intranasal route using in vivo phage display method to be used as CNS drug delivery carriers. Methods: To screen peptides with nose-to-brain transport capability, a 12-mer peptide library displayed on M13 bacteriophage was intranasally administered to anesthetized mice with subsequent recovery of the phage particles from the brain. The identified peptide sequences were analyzed using bioinformatics tools. Results: The results showed that intranasal transport of phage particles to the brain is independence of displayed peptide sequences due to random distribution of residues in different positions of isolated peptides. Nanoscale feature of bacteriophage particles may be responsible for nose-to-brain transport through olfactory epithelium. Conclusion: Taken together, the results open a route for designing phage-guided therapeutic systems as nanocarriers useful in intranasal brain targeting drug delivery.

Keywords: Phage display, blood brain barrier, nose-to-brain, peptide library, in vivo biopanning