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Nanoparticle brain delivery: a guide to verification methods.

Robert A Yokel1

  • 1Department of Pharmaceutical Sciences, University of Kentucky, Lexington, KY 40536-0596, USA.

Nanomedicine (London, England)
|January 31, 2020
PubMed
Summary
This summary is machine-generated.

Most studies showing nanoparticle (NP) brain entry use bulk brain analysis, which includes blood and vessels. True brain parenchymal NP entry is rarely observed, highlighting the importance of barrier integrity.

Keywords:
in situ brain perfusionblood–brain barrierblood–cerebrospinal fluid barrierbrain parenchymacapillary depletionconvection-enhanced deliverymicrodialysismousenanoparticlerat

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Area of Science:

  • Nanotechnology
  • Neuroscience
  • Toxicology

Background:

  • Many studies report nanoparticle (NP) brain entry using bulk brain analysis.
  • Bulk brain analysis includes blood, cerebrospinal fluid, and blood vessels, not solely brain tissue.
  • This approach may overestimate NP presence within the brain's functional tissue.

Purpose of the Study:

  • To critically evaluate methods used to assess NP brain entry.
  • To differentiate between bulk brain NP detection and actual brain parenchymal NP entry.
  • To review the anatomy and function of the blood-brain and blood-cerebrospinal fluid barriers.

Main Methods:

  • Review and critique of existing studies on NP brain entry.
  • Classification of results based on bulk brain versus brain parenchymal NP detection.
  • Comparison of NP timecourses in the brain, blood, and peripheral organs.

Main Results:

  • Most studies analyzing bulk brain tissue do not demonstrate NP entry into the brain parenchyma.
  • The integrity of the blood-brain and blood-cerebrospinal fluid barriers is crucial for NP brain parenchymal entry.
  • NP timecourses in the brain correlate with evidence of parenchymal entry.

Conclusions:

  • Distinguishing between bulk brain and brain parenchymal NP detection is critical for accurate assessment.
  • Current evidence suggests limited NP entry into the brain parenchyma under many experimental conditions.
  • Further research should focus on methods that specifically assess NP penetration beyond the brain barriers.