Novel and emerging strategies in drug delivery for overcoming the blood-brain barrier

Two decades of molecular research have revealed the presence of transporters and receptors expressed in the brain vascular endothelium that provide potential novel targets for the rational design of blood-brain barrier-penetrating drugs. In this review, we briefly introduce the reader to the molecular characteristics of the blood-brain barrier that make this one of the most important obstacles towards the development of efficacious CNS drugs. We highlight recent attempts to rationally target influx and bidirectional transport systems expressed on the brain endothelial cell and avoid the important obstacle presented in the form of efflux transporters. Many of these approaches are highly innovative and show promise for future human application. Some of these approaches, however, have revealed significant limitations and are critiqued in this review. Nonetheless, these combined efforts have left the field of CNS drug delivery better positioned for developing novel approaches towards the rational design of CNS-penetrating drugs.