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The effect of lipid nanoparticle PEGylation on neuroinflammatory response in mouse brain

Paper ID Volume ID Publish Year Pages File Format Full-Text
6387 488 2013 11 PDF Available
Title
The effect of lipid nanoparticle PEGylation on neuroinflammatory response in mouse brain
Abstract

Nanocarrier-based drug delivery systems have attracted wide interest for the treatment of brain disease. However, neurotoxicity of nanoparticle has limited their therapeutic application. Here we demonstrated that lipid nanoparticles (LNs) accumulated in the brain parenchyma within 3 h of intravenous injection to mice and persisted for more than 24 weeks, coinciding with a dramatic activation of brain microglia. Morphological characteristic of microglial activation also observed in LNs-treated Cx3cr1GFP/+ mice. In vivo study with two-photon confocal microscopy revealed abnormal Ca2+ waves in microglia following LNs injection. The correlated activation of caspase-1, IL-1β and neurovascular damage following LNs injection was attenuated in P2X7−/− mice. PEGylation of LNs reduced correlated nanoparticles aggregation. Moreover, PEGylation of LNs ameliorated the P2X7/caspase-1/IL-1β signalling-dependent microglia activation and neurovascular damage. In conclusion, PEGylation of LNs is a promising biomaterial for brain-targeted therapy that inhibits P2X7-dependent neuroinflammatory response.

Keywords
Lipid nanoparticles; PEGylation; Brain; Microglia; P2X7 receptor; Neuroinflammatory responseBBB, blood–brain barrier; BSA, bovine serum albumin; CaMKII, calcium/calmodulin-dependent kinase II; GFAP, glial fibrillary acidic protein; HtrA2, high temperature
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The effect of lipid nanoparticle PEGylation on neuroinflammatory response in mouse brain
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 34, Issue 32, October 2013, Pages 7960–7970
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us