Targeting the Choroid Plexus-CSF-Brain Nexus Using Peptides Identified by Phage Display
Drug delivery to the central nervous system requires the use of specific portals to enable drug entry into the brain and, as such, there is a growing need to identify processes that can enable drug transfer across both blood-brain and blood–cerebrospinal fluid barriers. Phage display is a powerful combinatorial technique that identifies specific peptides that can confer new activities to inactive particles. Identification of these peptides is directly dependent on the specific screening strategies used for their selection and retrieval. This chapter describes three selection strategies, which can be used to identify peptides that target the choroid plexus (CP) directly or for drug translocation across the CP and into cerebrospinal fluid.
Key wordsBlood-brain barrier Choroid plexus Choroid epithelial cells CNS targeting Library screening Combinatorial biology Blood-CSF barrier Drug translocation Ex vivo biopanning Ligand internalization Phage display Screening
This work was supported in part by the National Institutes of Health (USA) and the Biochemistry and Biotechnology Research Council (UK). The authors would like to thank Drs. Paul Kassner and David Larocca who first engineered the initial EGF-displayed phage that helped establish the feasibility of CP targeting, Dr. Michael Burg who helped identify CP-targeting peptides in peptide libraries, and Ms. Emelie Amburn and Dr. Karen Sims who assisted in their characterization.
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