Nose-to-brain co-delivery of repurposed simvastatin and BDNF synergistically attenuates LPS-induced neuroinflammation

Nose-to-brain co-delivery of repurposed simvastatin and BDNF synergistically attenuates LPS-induced neuroinflammation

Manickavasagam Dharani; Lin Li; Oyewumi Moses O

Nanomedicine: Nanotechnology, Biology, And Medicine

2019

2019-10-23

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 > striatum > 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.

Microglia; Nanoparticles; Drug repurposing; Polymersomes; Intranasal delivery

PMID: 31655202

Journal Article

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