Discovery of blood-brain barrier penetrating peptides by phage display technology to deliver biologics into the brain

Biologics as macromolecules can’t deliver to the brain without the blood-brain barrier (BBB) transport carriers. A phage display peptide library was employed to screen the BBB shuttling peptides by biopanning against an in vitro BBB model. We identified several novel and efficient BBB permeable peptides. A series of in vivo and in vitro studies were conducted to validate the capability of these peptides to transport the BBB and the brain extracellular matrix (ECM). The findings demonstrated that our peptides, Pep-3 and Pep-9 are able to shuttle across BBB and deliver to the brain parenchyma in vivo. Thereafter, Pep-9 was selected to develop IgG-Pep-9 conjugate formulation by click chemistry. In vivo delivery of IgG-Pep-9 indicated that Pep-9 can carry antibody molecules to transport BBB and deliver to the brain parenchyma.