We describe the build-up of biomaterial coatings based on polypeptide multilayers possessing anti-inflammatory properties. Poly(L-lysine) (PLL) and poly(L-glutamic acid) (PGA) are used as polypeptides, and piroxicam (Px) is used as the anti-inflammatory agent. In order to embed high enough amounts of Px, the drug is incorporated in the films in the form of complexes with a charged 6(A)-carboxymethylthio-beta-cyclodextrin (cCD). It is shown that this cyclodextrin can solubilize higher amounts of Px than the cyclodextrins used commercially. The anti-inflammatory properties are evaluated by determining the inhibition of TNFalpha production by human monocytic THP-1 cells stimulated with lipopolysaccharide (LPS) bacterial endotoxin. Using Fourier-transform (FT) Raman spectroscopy, we show that Px is mainly in the neutral form in cCD-Px complexes in solution, and that it remains biologically active under this form, whereas up to now only the zwitterionic form was reported to possess anti-inflammatory properties. When incorporated in PLL/PGA multilayers, Px in the cCD-Px complexes changes from the neutral to the zwitterionic form. It is shown that these films present anti-inflammatory properties, which can be delayed, and whose duration can be tuned by changing the film architecture.