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Salvaging brain ischemia by increasing neuroprotectant uptake via nanoagonist mediated blood brain barrier permeability enhancement

Paper ID Volume ID Publish Year Pages File Format Full-Text
5580 401 2015 12 PDF Available
Title
Salvaging brain ischemia by increasing neuroprotectant uptake via nanoagonist mediated blood brain barrier permeability enhancement
Abstract

Ischemic stroke is a leading cause of adult disability and cognitive impairment worldwide. Neuroprotective therapy aims to save neurons by impeding the deleterious ischemic insults. However, the low efficiency of the neuroprotectants crossing blood brain barrier (BBB) prevents their clinical translation. In this work, a nanoagonist (NA) was developed to enhance neuroprotectant uptake by specifically increasing BBB permeability in brain ischemia. This NA first targeted ischemic brain vasculatures, temporarily opened local BBB by activating adenosine 2A receptors, and up-regulated the neuroprotectant uptake in brain ischemia. This NA significantly increased the delivery of superoxide dismutase (SOD), a free radical scavenger, into mouse brain ischemia. The combined treatment of NA/SOD achieved a five-fold ischemic volume reduction rate compared to the animal models treated with SOD alone. Non-invasive magnetic resonance imaging (MRI) confirmed the ischemia targeted BBB opening, increased brain drug delivery efficiency and up-regulated therapeutic response during the combined NA/SOD treatment. Since the inefficient brain drug delivery is a general problem for the treatment of central nervous system (CNS) diseases, this work provides a novel strategy to deliver therapeutics by crossing BBB with high efficiency and targeting specificity.

Keywords
Ischemic stroke; Nanoagonist; Blood brain barrier; Adenosine receptor; Neuroprotective therapy
First Page Preview
Salvaging brain ischemia by increasing neuroprotectant uptake via nanoagonist mediated blood brain barrier permeability enhancement
Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 66, October 2015, Pages 9–20
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering