Non-covalent inclusion of ferulic acid with alpha-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 α-cyclodextrin by co-precipitation from an aqueous solution, and used 1H 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 α-CD hydrophobic cavity with the α,β-unsaturated part of the molecule and some of its aromatic skeleton. In proton chemical shift measurements of FA and α-cyclodextrins we determined the stoichiometry of the association complex (1:1) by Job's method, and its stability constant (K1:1 1162 ± 140 M-1) and described the molecular dynamics of the complex on the basis of theoretical studies. Encapsulation with α-cyclodextrin improves (i) the chemical stability of FA against UVB stress (10 MED [Minimal Erythemal Dose: 1 MED = 25 mJ/cm2 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).