Transporting therapeutics across the blood-brain barrier

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In 1996, we are half-way through the Decade of the Brain, yet we still have few effective treatments for major disorders of the central nervous system. These include affective disorders, epilepsy, neurodegenerative disorders, brain tumours, infections and HIV encephalopathy; sufferers far outnumber the morbidity of cancer or heart disease. Increased understanding of the pharmacology of the brain and its blood supply, and methods for rational drug design, are leading to potential new drug therapies based on highly specific actions on particular target sites, such as neurotransmitter receptors and uptake systems. These methods are capable of reducing the side effects that are common with more general treatments. However, all these treatments and potential treatments meet a formidable obstacle—the blood—brain barrier. In this article, we review the properties of this barrier that complicate drug delivery to the brain, and some of the most hopeful strategies for overcoming or bypassing the barrier in humans.

References (41)

  • GreigN.H.

    Drug entry into the brain and its pharmacological manipulation

  • SeeligA. et al.

    A method to determine the ability of drugs to diffuse through the blood—brain barrier

  • GreigN.H.

    Drug delivery to the brain by blood—brain barrier: circumvention and drug modification

  • LambertD.M.

    Synthesis and pharmacological properties of 2-[S-acetylthiorphan]-1,3-diacylaminopropan-2-ol derivatives as chimeric lipid drug carriers containing an enkephalinase inhibitor

    Pharm. Res.

    (1994)
  • van BreeJ.B.M.M.

    Stereoselective transport of baclofen across the blood—brain barrier in rats as determined by the unit impulse response methodology

    Pharm. Res.

    (1991)
  • TakadaY.

    Rapid high-affinity transport of a chemotherapeutic amino acid across the blood—brain barrier

    Cancer Res.

    (1992)
  • RapoportS.I.

    Drug delivery to the brain: barrier modification and drug modification methodologies

    NIDA Res. Monogr.

    (1992)
  • BegleyD.J.

    Peptides and the blood—brain barrier

  • WongS.L. et al.

    Distributional transport kinetics of zidovudine between plasma and brain extracellular fluid/cerebrospinal fluid in the rabbit: investigation of the inhibitory effect of probenecid utilizing microdialysis

    J. Pharmacol. Exp. Ther.

    (1993)
  • DykstraK.H.

    Microdialysis study of zidovudine (AZT) transport in rat brain

    J. Pharmacol. Exp. Ther.

    (1993)
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