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 Kodibagkar, Sarah Stabenfeldt

Research output: Contribution to journalArticle

10 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 2018

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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