The aim of this study was to examine the in vitro capacity of cyclodextrins to interfere on the beta-amyloid fibril formation; then, mucoadhesive microspheres containing cyclodextrins were prepared and characterised as nasal delivery system for brain targeting. Eight batches of microspheres containing chitosan or alginate loaded with beta-cyclodextrin or hydroxypropyl-beta-cyclodextrin in two different cyclodextrin to polymer ratios were produced by spray drying. The results show that none of the tested CDs has direct cellular toxicity and they protect the cell viability from beta-peptide. The microspheres prepared are characterised by small particle sizes, ability to absorb water and to delay the in vitro dissolution rate of the CDs; good ex vivo mucoadhesive properties of the formulations are assessed. The microsphere properties are influenced by the kind of polymer, of cyclodextrin and by cyclodextrin to polymer ratio used. In particular, the alginate formulation containing the higher cyclodextrin content shows the best performance.