Identification of a peptide that crosses the blood-cerebrospinal fluid barrier by phage display technology

Abstract

Treatments of brain diseases are heavily limited by the existence of the blood-brain barrier (BBB), which precludes efficient drug delivery to the brain. Compared with the BBB, drugs may have a better likelihood of reaching the brain via the cerebrospinal fluid (CSF) because of the lack of a barrier between the CSF and the brain. In this study, phage display technology was effectively applied to screen novel peptides as targeting motifs to transport drugs across the blood-cerebrospinal fluid barrier (BCSFB). We applied a phage seven-mer cyclic peptide library (Ph.D.-C7C™) intravenously to rats and later recovered phages from the CSF. After several rounds of screening, the candidate phages that could cross the BCSFB were enriched. Several bacteriophage clones from the final round were randomly selected and sequenced. A peptide sequence denoted as PMK, which was demonstrated to be able to cross the BCSFB via in vivo optical imaging analysis, could be used in the future for the construction of targeted drug delivery systems.

Keywords: Blood cerebrospinal fluid barrier; Brain delivery; Peptide; Phage display.