1. The effect of lipid nanoparticle PEGylation on neuroinflammatory response in mouse brain.
- Author
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Huang, Ji-yun, Lu, Ying-mei, Wang, Huan, Liu, Jun, Liao, Mei-hua, Hong, Ling-juan, Tao, Rong-rong, Ahmed, Muhammad Masood, Liu, Ping, Liu, Shuang-shuang, Fukunaga, Kohji, Du, Yong-zhong, and Han, Feng
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POLYETHYLENE glycol , *BRAIN disease treatment , *DRUG delivery systems , *INFLAMMATION , *LABORATORY mice , *NEUROTOXICOLOGY - Abstract
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 Cx3cr1 GFP/+ 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 P2X 7 −/− 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. [Copyright &y& Elsevier]
- Published
- 2013
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