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Cannabidiol (CBD) has previously been shown to inhibit inflammatory cytokine production in both in vitro and in vivo studies of neurodegenerative diseases. To date, the CBD treatment of these diseases by quantitative targeting directly to the brain is one of the greatest challenges. In this paper, we present a new particulate system capable of delivering CBD into the brain via the intranasal route. Intranasal administration of CBD-loaded starch nanoparticles resulted in higher levels of cannabidiol in the brain compared to an identically administered cannabidiol solution. The production and the characterization of starch-based nanoparticles was reported, as well as the evaluation of their penetration and anti-inflammatory activity in cells. Cannabidiol-loaded starch nanoparticles were prepared by crosslinking with divanillin, using the nanoprecipitation method. Evaluation of the anti-inflammatory activity in vitro was performed using the BV2 microglia cell line. The starch nanoparticles appeared under electron microscopy in clusters sized approximately 200 nm in diameter. In cultures of lipopolysaccharide-induced inflamed BV2 cells, the cannabidiol-loaded starch nanoparticles demonstrated low toxicity while effectively reducing nitric oxide production and IL-6 levels. The anti-inflammatory effect was comparable to that of a glucocorticoid. Starch-based nanoparticle formulations combined with intranasal administration may provide a suitable platform for efficacious cannabidiol delivery and activity in the central nervous system.

Cannabidiol-Loaded Nanoparticles Based on Crosslinked Starch: Anti-Inflammatory Activity and Improved Nose-to-Brain Delivery