Drug Delivery to the Brain Via the blood–brain Barrier: a Review of the Literature and Some Recent Patent Disclosures

Abstract

Delivery of drugs to the brain is challenging, not only for large biopharmaceutical molecules, but also for small organics, which are effluxed from the brain capillary endothelial cells. These cells constitute, in part, the selectively permeable blood-brain barrier. Progress is being made using delivery systems comprising a vector, a linker and cargo, which are purported to enter the brain via receptors on the luminal surface of the brain capillary endothelial cells. Unfortunately, from a delivery perspective, these receptors are not expressed only on brain capillary endothelial cells; so the approaches described in this review are for enhanced delivery to the brain, not for specific brain targeting. The inventions disclosed in patents relate to technologies to screen for new blood-brain barrier receptors and to identify new vectors, or describe systems that deliver cargoes to the brain via any blood-brain barrier receptor, or define specified peptide vectors that target a specific receptor. To date, only one of the technologies has reached early clinical trials and, as always, major challenges remain to be addressed.