Application of the Phage Display Technology for the Development of Peptide- mediated Drug Delivery Systems through the Blood-Brain Barrier

Abstract

The main obstacle to biopharmaceutical delivery in therapeutic concentration into the brain for treating neurological disorders is the presence of the Blood-Brain Barrier (BBB). The physiological process of Receptor-Mediated Transcytosis (RMT) to transport cargo through the brain endothelial cells toward brain parenchyma has prompted researchers to search for non-natural ligands that can be used to transport drugs across the BBB. Conjugation of drugs to RMT ligands would be an effective strategy for its delivery to the central nervous system. An attractive approach to identify novel transcytosing ligands is the screening by phage display combinatorial libraries. The main technology strength lies in the large variety of exogenous peptides or proteins displayed on the phage's surface. Here, we provide a mini-review of phage display technology using in vitro and in vivo BBB models for the development of peptide-mediated drug delivery systems.

Keywords: Phage display technology; blood-brain barrier; drug delivery; molecular trojan horse; receptor-mediated transcytosis; shuttle peptides.