Blood–brainbarrier disruption dictates nanoparticle accumulation following experimental brain injury

Vimala N. Bharadwaj, Rachel K. Rowe, Jordan Harrison, Chen Wu, Trent R Anderson, Jonathan Lifshitz, P. David Adelson, Vikram D. Kodibagkar, Sarah E. Stabenfeldt

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Clinically, traumatic brain injury (TBI) results in complex heterogeneous pathology that cannot be recapitulated in single pre-clinical animal model. Therefore, we focused on evaluating utility of nanoparticle (NP)-based therapeutics following three diffuse-TBI models: mildclosed-head injury (mCHI), repetitive-mCHI and midline-fluid percussion injury (FPI). We hypothesized that NP accumulation after diffuse TBI correlates directly with blood–brainbarrier permeability. Mice received PEGylated-NP cocktail (20-500 nm) (intravenously) after single- or repetitive-(1 impact/day, 5 consecutive days) CHI (immediately) and midline-FPI (1 h, 3 h and 6 h). NPs circulated for 1 h before perfusion/brain extraction. NP accumulation was analyzed using fluorescent microscopy in brain regions vulnerable to neuropathology. Minimal/no NP accumulation after mCHI/RmCHI was observed. In contrast, midlineFPI resulted in significant peak accumulation of up to 500 nm NP at 3 h post-injury compared to sham, 1 h, and 6 h groups in the cortex. Therefore, our study provides the groundwork for feasibility of NP-delivery based on NPinjection time and NPsize after mCHI/RmCHI and midline-FPI.

Original languageEnglish (US)
Pages (from-to)2155-2166
Number of pages12
JournalNanomedicine: Nanotechnology, Biology, and Medicine
Volume14
Issue number7
DOIs
StatePublished - Oct 1 2018

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Keywords

  • Blood-brain barrier
  • Drug delivery
  • Fluid percussion injury
  • Mild closed head injury
  • Nanoparticles
  • Optimal therapeutic window
  • Pharmacodynamics
  • Traumatic brain injury

ASJC Scopus subject areas

  • Bioengineering
  • Medicine (miscellaneous)
  • Molecular Medicine
  • Biomedical Engineering
  • Materials Science(all)
  • Pharmaceutical Science

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