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 alpha-cyclodextrin by co-precipitation from an aqueous solution, and used (1)H 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 alpha-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 alpha-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).
Anselmi
Cecilia
C
Dipartimento Farmaco Chimico Tecnologico, University of Siena, Via Aldo Moro, 53100 Siena, Italy. anselmic@unisi.it
Centini
Marisanna
M
Maggiore
Maria
M
Gaggelli
Nicola
N
Andreassi
Marco
M
Buonocore
Anna
A
Beretta
Giangiacomo
G
Facino
Roberto Maffei
RM
D000975:Antioxidants / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D003373:Coumaric Acids / Q000008:administration & dosage / Q000737:chemistry*; D004355:Drug Stability; D008027:Light; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D012995:Solubility; D014961:X-Ray Diffraction; D047391:alpha-Cyclodextrins / Q000008:administration & dosage / Q000032:analysis / Q000737:chemistry*
D000975:Antioxidants; D003373:Coumaric Acids; D047391:alpha-Cyclodextrins; C004999:ferulic acid; C032613:alpha-cyclodextrin