Non-covalent inclusion of ferulic acid with α-cyclodextrin improves photo-stability and delivery:: NMR and modeling studies

Ferulic acid (FA) is a highly effective antioxidant and photo-protective agent, already approved in Japan as a sunscreen, but it is poorly suited for cosmetic application because of its low physicochemical stability. We prepared the inclusion complex of FA with alpha-cyclodextrin by co-precipitation from an aqueous solution, and used H-1 NMR and molecular dynamics to investigate the most probable structure of the inclusion complex. In rotating frame nuclear Overhouser effect spectroscopy (ROESY) experiments FA penetrated the alpha-CD hydrophobic cavity with the alpha,beta-unsaturated part of the molecule and some of its aromatic skeleton. In proton chemical shift measurements of FA and a-cyclodextrins we determined the stoichiometry of the association complex (1:1) by Job's method, and its stability constant (K-1:1 1162 +/- 140 M-1) and described the molecular dynamics of the complex on the basis of theoretical studies. Encapsulation with a-cyclodextrin improves (i) the chemical stability of FA against UVB stress (10 MED [Minimal Erythemal Dose: 1 MED = 25 mJ/cm(2) for skin phototype II: 30]), since no degradation products are formed after irradiation, and (ii) the bioavailability of FA on the skin, slowing its delivery (Strainer cell model). (C) 2007 Elsevier B.V. All rights reserved.