Non-Invasive Brain Targeted Delivery of Cannabidiol for Alleviating Neuroinflammatory Disease.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 42051066.
- Also identified by DOI 10.1002/adma.202518697.
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Abstract
Chronic neuroinflammation is a known etiopathogenic factor in neurodegenerative disease. While cannabidiol (CBD) has demonstrated anti-inflammatory effects, unfavorable pharmacokinetics and poor blood-brain barrier (BBB) permeability lead to low brain exposure. Here, we greatly improve the efficacy of CBD to treat neuroinflammation by incorporating CBD in a BBB-permeable glucose nanoparticle (GNPs) that by design also incorporates tissue-targeting moieties and uses reactive oxygen species responsive polymer to selectively target neuroinflammatory lesions. We achieved a high drug concentration over 20 times higher than naked cargo and demonstrate potent therapeutic effects in two mouse models of neuroinflammatory disease. Mechanistically, disease amelioration resulted from repolarizing microglia from the neurotoxic M1 to the neuroprotective M2 phenotype, leading to neuronal cell regeneration by enhanced secretion of brain derived neurotropic and anti-inflammatory factors. Our approach for brain targeted CBD delivery may provide a versatile platform for treating other CNS disorders characterized by neuroinflammation.