Targeting choroid plexus epithelia and ventricular ependyma for drug delivery to the central nervous system
1 School of Experimental Medicine and Dentistry, University of Birmingham, Edgbaston, UK
2 Division of Trauma, Burns and Surgical Critical Care, Department of Surgery, University of California San Diego, San Diego Calif. USA
3 School of Pharmaceutical Sciences, Tohoku University, Japan
4 Neurosurgery and Neuropathology, Rhode Island Hospital of Brown University, Providence RI USA
BMC Neuroscience 2011, 12:4 doi:10.1186/1471-2202-12-4Published: 7 January 2011
Because the choroid plexus (CP) is uniquely suited to control the composition of cerebrospinal fluid (CSF), there may be therapeutic benefits to increasing the levels of biologically active proteins in CSF to modulate central nervous system (CNS) functions. To this end, we sought to identify peptides capable of ligand-mediated targeting to CP epithelial cells reasoning that they could be exploited to deliver drugs, biotherapeutics and genes to the CNS.
A peptide library displayed on M13 bacteriophage was screened for ligands capable of internalizing into CP epithelial cells by incubating phage with CP explants for 2 hours at 37C and recovering particles with targeting capacity.
Three peptides, identified after four rounds of screening, were analyzed for specific and dose dependant binding and internalization. Binding was deemed specific because internalization was prevented by co-incubation with cognate synthetic peptides. Furthermore, after i.c.v. injection into rat brains, each peptide was found to target phage to epithelial cells in CP and to ependyma lining the ventricles.
These data demonstrate that ligand-mediated targeting can be used as a strategy for drug delivery to the central nervous system and opens the possibility of using the choroid plexus as a portal of entry into the brain.