Localized delivery of low-density lipoprotein docosahexaenoic acid nanoparticles to the rat brain using focused ultrasound

Rohit S. Mulik, Chenchen Bing, Michelle Ladouceur-Wodzak, Imalka Munaweera, Rajiv Chopra, Ian R. Corbin

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Focused ultrasound exposures in the presence of microbubbles can achieve transient, non-invasive, and localized blood-brain barrier (BBB) opening, offering a method for targeted delivery of therapeutic agents into the brain. Low-density lipoprotein (LDL) nanoparticles reconstituted with docosahexaenoic acid (DHA) could have significant therapeutic value in the brain, since DHA is known to be neuroprotective. BBB opening was achieved using pulsed ultrasound exposures in a localized brain region in normal rats, after which LDL nanoparticles containing the fluorescent probe DiR (1,1'-Dioctadecyl-3,3,3',3'-Tetramethylindotricarbocyanine Iodide) or DHA were administered intravenously. Fluorescent imaging of brain tissue from rats administered LDL-DiR demonstrated strong localization of fluorescence signal in the exposed hemisphere. LDL-DHA administration produced 2 × more DHA in the exposed region of the brain, with a corresponding increase in Resolvin D1 levels, indicating DHA was incorporated into cells and metabolized. Histological evaluation did not indicate any evidence of increased tissue damage in exposed brain regions compared to normal brain. This work demonstrates that localized delivery of DHA to the brain is possible using systemically-administered LDL nanoparticles combined with pulsed focused ultrasound exposures in the brain. This technology could be used in regions of acute brain injury or as a means to target infiltrating tumor cells in the brain.

Original languageEnglish (US)
Pages (from-to)257-268
Number of pages12
JournalBiomaterials
Volume83
DOIs
StatePublished - Mar 1 2016

Fingerprint

Lipoproteins
Docosahexaenoic Acids
LDL Lipoproteins
Nanoparticles
Rats
Brain
Ultrasonics
Acids
Blood-Brain Barrier
Microbubbles
Tissue
Iodides
Fluorescent Dyes
Neuroimaging
Brain Injuries
Fluorescence
Tumors
Technology
Cells

Keywords

  • Bloodbrain-barrier
  • Brain
  • Focused ultrasound
  • Lipoprotein
  • Nanoparticle
  • Omega-fatty acid

ASJC Scopus subject areas

  • Biomaterials
  • Bioengineering
  • Ceramics and Composites
  • Mechanics of Materials
  • Biophysics

Cite this

Localized delivery of low-density lipoprotein docosahexaenoic acid nanoparticles to the rat brain using focused ultrasound. / Mulik, Rohit S.; Bing, Chenchen; Ladouceur-Wodzak, Michelle; Munaweera, Imalka; Chopra, Rajiv; Corbin, Ian R.

In: Biomaterials, Vol. 83, 01.03.2016, p. 257-268.

Research output: Contribution to journalArticle

Mulik, Rohit S. ; Bing, Chenchen ; Ladouceur-Wodzak, Michelle ; Munaweera, Imalka ; Chopra, Rajiv ; Corbin, Ian R. / Localized delivery of low-density lipoprotein docosahexaenoic acid nanoparticles to the rat brain using focused ultrasound. In: Biomaterials. 2016 ; Vol. 83. pp. 257-268.
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