Pharmacokinetics of Drug Delivery Past the Blood-Brain Barrier

John M. McGregor, Nancy Doolittle, Emily Youngers, Susan D. Bell, Edward A. Neuwelt

Research output: Chapter in Book/Report/Conference proceedingChapter

1 Scopus citations

Abstract

The blood-brain barrier (BBB) is a complex anatomic and physiologic structure made up of associated structures known as the neurovascular unit (NVU). The NVU protects the sensitive central nervous system (CNS) from molecules with potential toxic or unwanted neurologic effects. These protective mechanisms have prevented introduction of therapeutic drugs for treatment of diseases of the CNS; however, extensive study of the BBB has identified a wide variety of opportunities to exploit it in future drug development. Efforts to accurately measure the ability of medications to cross the NVU into positions of therapeutic benefit are varied and are, in many ways, complementary. Certain drug modifications opened the door to enhanced therapeutics, but also to unexpected CNS toxicities and unanticipated concentrations and toxicities in systemic organ systems. Osmotic BBB disruption with intra-arterial mannitol has been well characterized and clinically applied for years as a successful method for delivery of CNS therapeutics across the NVU. Preclinical analysis, clinical applications of drug delivery and safety, and therapeutic benefit with minimal toxicities have evolved over the years thanks to preclinical and translational studies of the effects of BBB disruption. Future developments will shed light on opportunities for targeted drug delivery using known pathways through the NVU, with continued emphasis on specificity, safety, and therapeutic benefit.

Original languageEnglish (US)
Title of host publicationNervous System Drug Delivery
Subtitle of host publicationPrinciples and Practice
PublisherElsevier
Pages57-72
Number of pages16
ISBN (Electronic)9780128139981
ISBN (Print)9780128139974
DOIs
StatePublished - Jun 25 2019

Keywords

  • Blood-brain barrier
  • Cell-mediated transport
  • Convection-enhanced delivery
  • Drug delivery
  • Endothelial cell
  • Focused ultrasound
  • Mannitol
  • Neurovascular unit
  • Pharmacokinetics
  • Receptor-mediated transport
  • Tight junctions

ASJC Scopus subject areas

  • Medicine(all)

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