Evaluating differential nanoparticle accumulation and retention kinetics in a mouse model of traumatic brain injury via Ktrans mapping with MRI

Hunter A. Miller, Alexander W. Magsam, Aria W. Tarudji, Svetlana Romanova, Laura Weber, Connor C. Gee, Gary L. Madsen, Tatiana K. Bronich, Forrest M. Kievit

Research output: Contribution to journalArticle

Abstract

Traumatic brain injury (TBI) is a leading cause of injury-related death worldwide, yet there are no approved neuroprotective therapies that improve neurological outcome post-injury. Transient opening of the blood-brain barrier following injury provides an opportunity for passive accumulation of intravenously administered nanoparticles through an enhanced permeation and retention-like effect. However, a thorough understanding of physicochemical properties that promote optimal uptake and retention kinetics in TBI is still needed. In this study, we present a robust method for magnetic resonance imaging of nanoparticle uptake and retention kinetics following intravenous injection in a controlled cortical impact mouse model of TBI. Three contrast-enhancing nanoparticles with different hydrodynamic sizes and relaxivity properties were compared. Accumulation and retention were monitored by modelling the permeability coefficient, Ktrans, for each nanoparticle within the reproducible mouse model. Quantification of Ktrans for different nanoparticles allowed for non-invasive, multi-time point assessment of both accumulation and retention kinetics in the injured tissue. Using this method, we found that 80 nm poly(lactic-co-glycolic acid) nanoparticles had maximal Ktrans in a TBI when injected 3 hours post-injury, showing significantly higher accumulation kinetics than the small molecule, Gd-DTPA. This robust method will enable optimization of administration time and nanoparticle physicochemical properties to achieve maximum delivery.

Original languageEnglish (US)
Article number16099
JournalScientific reports
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2019

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Nanoparticles
Wounds and Injuries
Gadolinium DTPA
Hydrodynamics
Traumatic Brain Injury
Blood-Brain Barrier
Intravenous Injections
Permeability
Magnetic Resonance Imaging

ASJC Scopus subject areas

  • General

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Evaluating differential nanoparticle accumulation and retention kinetics in a mouse model of traumatic brain injury via Ktrans mapping with MRI. / Miller, Hunter A.; Magsam, Alexander W.; Tarudji, Aria W.; Romanova, Svetlana; Weber, Laura; Gee, Connor C.; Madsen, Gary L.; Bronich, Tatiana K.; Kievit, Forrest M.

In: Scientific reports, Vol. 9, No. 1, 16099, 01.12.2019.

Research output: Contribution to journalArticle

Miller, Hunter A. ; Magsam, Alexander W. ; Tarudji, Aria W. ; Romanova, Svetlana ; Weber, Laura ; Gee, Connor C. ; Madsen, Gary L. ; Bronich, Tatiana K. ; Kievit, Forrest M. / Evaluating differential nanoparticle accumulation and retention kinetics in a mouse model of traumatic brain injury via Ktrans mapping with MRI. In: Scientific reports. 2019 ; Vol. 9, No. 1.
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