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While cannabidiol (CBD) has demonstrated anti\u2010inflammatory effects, unfavorable pharmacokinetics and poor blood\u2010brain 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\u2010permeable glucose nanoparticle (GNPs) that by design also incorporates tissue\u2010targeting 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\u2010inflammatory factors. Our approach for brain targeted CBD delivery may provide a versatile platform for treating other CNS disorders characterized by neuroinflammation.<\/jats:p>","DOI":"10.1002\/adma.202518697","type":"journal-article","created":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T07:06:30Z","timestamp":1777446390000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Non\u2010Invasive Brain Targeted Delivery of Cannabidiol for Alleviating Neuroinflammatory Disease"],"prefix":"10.1002","volume":"38","author":[{"given":"Yibin","family":"Wang","sequence":"first","affiliation":[{"name":"Henan International Joint Laboratory of Nanobiomedicine, the Second Clinical Medical College School of Life Sciences Henan University Kaifeng Henan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yundong","family":"Li","sequence":"additional","affiliation":[{"name":"Henan International Joint Laboratory of 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