Abstract: Delivery of therapeutic agents into the brain is a major challenge in central nervous\nsystem drug development. The blood-brain barrier (BBB) prevents access of biotherapeutics to\ntheir targets in the central nervous system and, therefore, prohibits the effective treatment of many\nneurological disorders. To find blood-brain barrier shuttle peptides that could target therapeutics\nto the brain, we applied a phage display technology on a primary endothelial rat cellular model.\nTwo identified peptides from a 12 mer phage library, GLHTSATNLYLH and VAARTGEIYVPW,\nwere selected and their permeability was validated using the in vitro BBB model. The permeability\nof peptides through the BBB was measured by ultra-performance liquid chromatography-tandem\nmass spectrometry coupled to a triple-quadrupole mass spectrometer (UHPLC-MS/MS). We showed\nhigher permeability for both peptides compared to N-C reversed-sequence peptides through in vitro\nBBB: for peptide GLHTSATNLYLH 3.3*10-7 cm/s and for peptide VAARTGEIYVPW 1.5*10-6\ncm/s. The results indicate that the peptides identified by the in vitro phage display technology could\nserve as transporters for the administration of biopharmaceuticals into the brain. Our results also\ndemonstrated the importance of proper BBB model for the discovery of shuttle peptides through\nphage display libraries.
Loading....