Identification of peptide ligands for targeting to the blood-brain barrier

van Rooy, Inge; Cakir-Tascioglu, Serpil; Couraud, Pierre-Olivier; Romero, Ignacio A.; Weksler, Babette; Storm, Gert; Hennink, Wim E.; Schiffelers, Raymond M. and Mastrobattista, Enrico (2010). Identification of peptide ligands for targeting to the blood-brain barrier. Pharmaceutical Research, 27(4) pp. 673–682.

DOI: https://doi.org/10.1007/s11095-010-0053-6

Abstract

Purpose
Transport of drugs to the brain is limited by the blood-brain barrier. New, specific brain endothelium ligands can facilitate brain-specific delivery of drugs.
Methods
We used phage display in an in situ brain perfusion model to screen for new brain endothelium peptide ligands.
Results
Two phage clones, displaying 15 amino acid-peptides (GLA and GYR) that were selected for brain binding in the mouse model, showed significant binding to human brain endothelium (hCMEC/D3), compared to a random control phage. This binding was not seen for other human endothelial cells (HUVEC). Binding to hCMEC/D3 cells was dose dependent. When phage GLA and GYR were individually perfused through the murine brain, their ability to bind to the brain was 6-fold (GLA) and 5-fold (GYR) higher than the control phage. When compared to lung perfusion, phage showed an 8.5-fold (GYR) and 48-fold (GLA) preference for brain over lung compared to the control.
Conclusions
These results indicate that two new peptide ligands have been identified that may be used for specific targeting of drugs to the blood-brain barrier.

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