Targeting blood-brain barrier changes during inflammatory pain: An opportunity for optimizing CNS drug delivery

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

The blood-brain barrier (BBB) is the most significant obstacle to effective CNS drug delivery. It possesses structural and biochemical features (i.e., tight-junction protein complexes and, influx and efflux transporters) that restrict xenobiotic permeation. Pathophysiological stressors (i.e., peripheral inflammatory pain) can alter BBB tight junctions and transporters, which leads to drug-permeation changes. This is especially critical for opioids, which require precise CNS concentrations to be safe and effective analgesics. Recent studies have identified molecular targets (i.e., endogenous transporters and intracellular signaling systems) that can be exploited for optimization of CNS drug delivery. This article summarizes current knowledge in this area and emphasizes those targets that present the greatest opportunity for controlling drug permeation and/or drug transport across the BBB in an effort to achieve optimal CNS opioid delivery.

Original languageEnglish (US)
Pages (from-to)1015-1041
Number of pages27
JournalTherapeutic Delivery
Volume2
Issue number8
DOIs
StatePublished - Aug 2011

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Blood-Brain Barrier
Pain
Pharmaceutical Preparations
Opioid Analgesics
Tight Junction Proteins
Tight Junctions
Xenobiotics
Analgesics

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

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abstract = "The blood-brain barrier (BBB) is the most significant obstacle to effective CNS drug delivery. It possesses structural and biochemical features (i.e., tight-junction protein complexes and, influx and efflux transporters) that restrict xenobiotic permeation. Pathophysiological stressors (i.e., peripheral inflammatory pain) can alter BBB tight junctions and transporters, which leads to drug-permeation changes. This is especially critical for opioids, which require precise CNS concentrations to be safe and effective analgesics. Recent studies have identified molecular targets (i.e., endogenous transporters and intracellular signaling systems) that can be exploited for optimization of CNS drug delivery. This article summarizes current knowledge in this area and emphasizes those targets that present the greatest opportunity for controlling drug permeation and/or drug transport across the BBB in an effort to achieve optimal CNS opioid delivery.",
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