Journal
NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
Volume 23, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.nano.2019.102107
Keywords
Nanoparticles; Microglia; Polymersomes; Intranasal delivery; Drug repurposing
Funding
- Thomases family endowment
- Dr. Colene Young Memorial fund
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A therapeutic strategy that can combat the multifaceted nature of neuroinflammation pathology was investigated. Thus, we fabricated PEG-PdLLA polymersomes and evaluated the efficacy in co-delivery of simvastatin (Sim, as a repurposed anti-inflammatory agent) with brain derived neurotrophic factor (BDNF, as an exogeneous trophic factor supplementation). Using LPS model of neuroinflammation, intranasal administration of combination drug-loaded polymersomes (containing both Sim and BDNF; Sim-BDNF-Ps) markedly down-regulated brain levels of cytokines compared to free drug and single-drug-loaded polymersomes. Further, Sim-BDNF-Ps effectively replenished brain level of BDNF that was depleted following neuroinflammation, resulting in a 2-fold BDNF increase versus untreated LPS control group. We found out that the efficiency of the combination drug-loaded polymersomes to suppress microglia activation in brain regions followed the order: frontal cortex N striatum N hippocampus. Our findings indicated that Sim-BDNF-Ps could effectively inhibit microglial-mediated inflammation as well as potentially resolve the neurotoxic microenvironment that is often associated with neuroinflammation. (c) 2019 Elsevier Inc. All rights reserved.
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