Caffeic acid is a natural antioxidant, largely distributed in plant tissues and food sources, possessing anti-inflammatory, antimicrobial, and anticarcinogenic properties. The object of this investigation was the development of a formulation for caffeic acid cutaneous administration. To this aim, caffeic acid has been loaded in solid lipid nanoparticles by hot homogenization and ultrasonication, obtaining aqueous dispersions with high drug encapsulation efficiency and 200 nm mean dimension, as assessed by photon correlation spectroscopy. With the aim to improve the consistence of the aqueous nanodispersions, different types of polymers have been considered. Particularly, poloxamer 407 and hyaluronic acid gels containing caffeic acid have been produced and characterized by X-ray and rheological analyses. A Franz cell study enabled to select poloxamer 407, being able to better control caffeic acid diffusion. Thus, a nanoparticulate gel has been produced by addition of poloxamer 407 to nanoparticle dispersions. Notably, caffeic acid diffusion from nanoparticulate gel was eight-fold slower with respect to the aqueous solution. In addition, the spreadability of nanoparticulate gel was suitable for cutaneous administration. Finally, the antioxidant effect of caffeic acid loaded in nanoparticulate gel has been demonstrated by ex-vivo evaluation on human skin explants exposed to cigarette smoke, suggesting a protective role exerted by the nanoparticles.
Keywords: caffeic acid; cigarette smoke; poloxamer; small angle X-ray scattering; solid lipid nanoparticles.