ABSTRACT
This chapter focuses on nonviral nucleic acid vehicles and the barriers to their delivery to the central nervous system (CNS). Ligands for receptor- and carrier-mediated transport to the CNS are presented in the context of vehicles and strategies which have been successfully used to overcome delivery barriers in vivo. The increasing prevalence of CNS-related diseases urgently requires the development of biological drugs such as proteins, antibodies, peptides or nucleic acids which can cross the blood-brain barrier. Free nucleic acids cannot use any of the mentioned carrier-mediated transport, receptor-mediated transport or adsorptive-mediated transcytosis pathways, which is why they must be formulated with suitable carriers for brain delivery. A fundamental issue of brain delivery is the optimal size of nanoparticles, regardless of their decoration with targeting ligands. Endogenous transport systems of the cerebral vasculature include carrier-mediated transporters such as glucose and amino acid carriers.
