Download Characterisation of peptides that cross the blood brain barrier, as

Characterisation of peptides that cross the blood brain barrier, as lead
molecules for the development of drug delivery vectors.
Yves Molino, Marion David, Aude Fortoul, Patrick Vlieghe and Michel Khrestchatisky
Neurobiologie des Interactions Cellulaires et Neurophysiopathologie (NICN), UMR 6184,
CNRS-Université Aix Marseille II, IFR Jean Roche ; VECT-HORUS S.A.S. Marseille,
France.
The central nervous system (CNS, brain and spinal cord) has very specific features: the
vascular systems of the CNS which separate blood from the nervous tissue constitute highly
impermeable physiological barriers known as the blood brain barrier (BBB) and bloodcerebrospinal fluid barrier (B-CSFB). These barriers protect efficiently the CNS from toxic
molecules, viral and bacterial infections, but also restrict very efficiently the passage from
blood to the nervous tissue of drugs or molecules with proven therapeutic potential. Research
in neurobiology has enabled the characterization of new classes of very promising therapeutic
agents mainly represented by large size molecules, peptides, recombinant proteins, fusion
proteins, enzymes, cytokines and neurotrophic factors. Unfortunately, for the vast majority,
these large molecules do not cross the physiological barriers. Our global objective is the
development of collections of vectors dedicated to enhancing drug delivery to the diseased
CNS. Using in vitro models of the BBB cultivated in a double chamber system and 2D
cultures of human microvascular brain endothelial cells, we have developed a high throughput
screening strategy of peptide libraries to characterise peptides that bind to endothelial cells,
that undergo endocytosis and transcytosis and that cross the BBB in vivo.