Phage selection on cell models for BBB penetrating peptides. (A) Phage library selection for BBB-permeable cyclic heptapeptides with the hCMEC/D3 cell permeability assay. Phage library was added on the apical side, and phages were collected from the basal side to penetrate through the hCMEC/D3 cell monolayer. (B) Permeability assay with identified phage clones that crossed the in vitro monkey and rat co-culture BBB models. The black box represents an enlarged view of the number of phage penetrations to the basal side in the first 5 min. Closed circle, SLS phage; closed triangle, NTG phage; open circle, control phage. (C) Distribution of SLS-phages in the mouse brain after intravenous administration (phage, green; blood vessel, red; nuclei, blue). (D) Contents of 10% SLS-liposomes and control liposome in brain and plasma after intravenous administration into the mice. Reprinted with permission from 98. Copyright 2020 ELSEVIER.