New insights to target nano-drug delivery systems to the central nervous system

Neurological disorders affect the structure and/or the function of the brain or the spinal cord, which together form the central nervous system (CNS). The blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB) represent major hurdles for the effective and timeous delivery of therapeutic agents to the CNS. It has been estimated that more than 98% of small-molecule and ~100% of large-molecule neurotherapeutics cannot cross these barriers to reach concentrations within the therapeutic window in the CNS. Crossing the BBB and the BCSFB remains challenging in the development of drugs for the treatment of CNS diseases. In this scenario, the design of novel strategies to increase drug bioavailability in the CNS is called for. In this talk, I will introduce new strategies investigated in my laboratory to actively-target neurotherapeutics to the CNS, such as the surface-modification of nanoparticles with highly biostable peptide shuttles or peptide targeting sequences and the exploitation of the folic acid receptor pathway in the choroid plexus epithelium. In addition, our recent advances in the elucidation of cellular pathways involved in the nose-to-brain transport of nanoparticles will be overviewed.