Plant-Derived Nanovesicle Enhanced Microribonucleic Acid (MicroRNA) Transfer from Nasal Cavity to the Brain

The nasal-to-brain route for drug delivery is potentially useful for the treatment of brain disorders. Not only chemically modified molecules but also nanosized carrier vesicles, such as cell culture-derived exosomes, as small molecules, could be delivered via this route. The focus of the present study was to evaluate the potential of vesicular plant-derived nanoparticles (PDNPs), which have been identified as multivesicular bodies, for transporting molecules via the nasal-to-brain route. PDNPs were isolated from the edible parts of onion (<i>Allium cepa</i>), cherry tomato (<i>Lycopersicon esculentum</i> <i>var. cerasiforme</i>), Delaware grape (<i>Vitis labrusca</i> "<i>Delaware</i>"), and grapefruit (<i>Citrus × paradisi</i>) using commercial kits without ultracentrifugation. Recombinant exogenous microRNA (cel-miR-39) was encapsulated into PDNPs by electroporation. Cel-miR-39-incorporated PDNPs were administered to adult male C57BL/6J mice via intranasal instillation or intravenous injection, and then tissue samples were collected. Cel-miR-39 transportation efficiency was evaluated by quantitative RT-PCR. Intranasal instillation was found to be more effective than intravenous injection for microRNA delivery to the brain. The onion-derived nanoparticle was the most effective transporter of microRNA to the olfactory bulb and caudal brain. The transportation potential and kinetics of other molecules (therapeutic drugs) using onion-derived nanoparticles are of future interest.