Quercetin, a flavonoid with possible neuroprotective action has been recently suggested for the early-stage treatment of Alzheimer’s disease. The low solubility and extended first pass effect render quercetin unsuitable for oral administration. Alternatively, brain targeting is more feasible with nasal delivery, by-passing, non-invasively, Blood-Brain Barrier and ensuring rapid onset of action. Aiming to increase quercetin’s disposition into brain, nasal powders consisting of quercetin-cyclodextrins (methyl-β-cyclodextrin and hydroxypropyl-β-cyclodextrin) lyophilizates blended with spray-dried microparticles of mannitol/lecithin were prepared. Quercetin’s solubility at 37°C and pH 7.4 was increased 19-35 times when complexed with cyclodextrins. Blending lyophilizates in various ratios with mannitol/lecithin microparticles, results in powders with improved morphological characteristics as observed by X-ray Diffraction and Scanning Electron Microscopy analysis. In vitro characterization of these powders using Franz cells, revealed rapid dissolution and permeation 17 (methyl-β-cyclodextrin) to 48 (hydroxypropyl-β-cyclodextrin) times higher than that of pure quercetin. Ex vivo powders’ transport across rabbit nasal mucosa was found more efficient in comparison with the pure quercetin. The overall better performance of quercetin-hydroxypropyl-β-cyclodextrin powders is confirmed by ex vivo experiments revealing amount of quercetin permeated ranging from 0.03±0.01 to 0.22±0.05 μg/cm2 for hydroxypropyl-β-cyclodextrin and 0.022±0.01 to 0.17±0.04 μg/cm2 for methyl-β-cyclodextrin powders, while the permeation of pure quercetin was negligible.
Papakyriakopoulou P, Manta K, Kostantini C, Kikionis S, Banella S, Ioannou E, Christodoulou E, Rekkas DM, Dallas P, Vertzoni M, Valsami G, Colombo G. Nasal powders of quercetin-β-cyclodextrin derivatives complexes with mannitol/lecithin microparticles for Nose-to-Brain delivery: In vitro and ex vivo evaluation. Int J Pharm. 2021 Aug 16:121016. doi: 10.1016/j.ijpharm.2021.121016. Epub ahead of print. PMID: 34411652.
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