Drug Permeability: From the Blood-Brain Barrier to the Peripheral Nerve Barriers.

Drug delivery into the peripheral nerves and nerve roots has important implications for effective local anesthesia and treatment of peripheral neuropathies and chronic neuropathic pain. Similar to drugs that need to cross the blood-brain barrier (BBB) and blood-spinal cord barrier (BSCB) to gain access to the central nervous system (CNS), drugs must cross the peripheral nerve barriers (PNB), formed by the perineurium and blood-nerve barrier (BNB) to modulate peripheral axons. Despite significant progress made to develop effective strategies to enhance BBB permeability in therapeutic drug design, efforts to enhance drug permeability and retention in peripheral nerves and nerve roots are relatively understudied. Guided by knowledge describing structural, molecular and functional similarities between restrictive neural barriers in the CNS and peripheral nervous system (PNS), we hypothesize that certain CNS drug delivery strategies are adaptable for peripheral nerve drug delivery. In this review, we describe the molecular, structural and functional similarities and differences between the BBB and PNB, summarize and compare existing CNS and peripheral nerve drug delivery strategies, and discuss the potential application of selected CNS delivery strategies to improve efficacious drug entry for peripheral nerve disorders.

Déclaration de conflit d'intérêts

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. U.W. reports research grants from the US National Institutes of Health. She serves on the External Consultant Board for the “NIH Preclinical Screening Platform for Pain”, a novel pre-clinical pain therapy screening platform that has been launched at the National Institute for Neurological Disorders and Stroke in the U.S. In her capacity as a special government employee of the US Food and Drug Administration (FDA), she has served as a voting member of the FDA Anesthetic and Analgesic Drug Products Advisory Committee. In the past 3 years she has received compensation for serving on advisory boards or for consulting activities for Aphrodite Health Inc., Wilmington, DE, Avenue Therapeutics Inc., New York, NY, Bayer Aktiengesellschaft, Leverkusen, Germany, and Biohaven Pharmaceuticals, New Haven, CT, all unrelated to the submitted work. EEU reports a non-exclusive commercial license (held by Baylor Licensing Group) for simian virus-40 large T-antigen immortalized human endoneurial endothelial cell line and has received royalties from Springer Science + Business Media for an edited book on laboratory protocols that describes a flow-dependent in vitro human BNB leukocyte trafficking assay.