Peripheral nerve barrier and its implications for drug delivery

Drug delivery to the peripheral nervous system (PNS) is limited by the peripheral nerve barrier (PNB). Here, we holistically review the structure and anatomy of the PNB, differences and similarities between PNS and CNS barriers, methods to assess peripheral nerve penetration, peripheral nerve penetration for small molecules and macromolecules, and implications to deliver therapeutics to peripheral nerves. Important findings include: (i) the peripheral nerve is generally more permeable to small molecules than the brain; (ii) the PNB can effectively restrict the transport of macromolecules. These insights should help identify therapeutics to treat diseases with targets located at peripheral nerves.