Barriers to drug delivery for brain trauma

Abstract

One of the most opposing barriers-both literally and figuratively- challenging the translational advancement of therapeutics targeting brain trauma involves effective delivery of potentially neuroprotective agents to the damaged brain. Aspects distinguishing delivery of drugs to the injured brain relative to other tissues include: (1) several unique physical features of the blood-brain barrier (BBB) vs. other blood-tissue barriers; (2) added diffusion distance associated with astrocyte swelling (in addition to interstitial edema) away from the therapeutic target; and (3) membrane transporters at both the BBB and blood-CSF barriers (BCSFB), such as ATP-binding cassette (ABC) transporters, organic anion transporters (OAT), and organic anion transporting peptides (OATP) that have the capacity to move drug substrates out of the brain, actively reducing brain bioavailability. While these "barriers" represent unique challenges to the development of efficacious neuroprotective agents for the treatment of traumatic brain injury (TBI), recent pharmacological advancements provide an optimistic outlook for designing strategies that impact outcome for victims of TBI in the near future.