International Journal of Pharmaceutics 199 (2000) 39 – 47 In vitro and in vivo evaluation of caffeic and ferulic acids as topical photoprotective agents Antonella Saija a, *, Antonio Tomaino b , Domenico Trombetta b , Anna De Pasquale b , Nicola Uccella c , Tony Barbuzzi d , Donatella Paolino d , Francesco Bonina d a Department of Pharmacology of Natural Substances and General Physiology, Uniersity of Rome ‘La Sapienza’, Rome, Italy b Department Farmaco -Biologico, School of Pharmacy, Uniersity of Messina, Contrada Annunziata, 98168 Messina, Italy c CIRASAIA, Uniersity of Calabria, Arcaacata di Rende, Italy d Department of Pharmaceutical Sciences, Uniersity of Catania, Catania, Italy Received 6 October 1999; received in revised form 4 January 2000; accepted 26 January 2000 Abstract Topically-applied antioxidant drugs represent a successful strategy for protecting the skin against UV-mediated oxidative damage. However, they can afford to the skin a satisfactory photoprotection only if able to permeate through the stratum corneum and thus to reach deeper cutaneous layers. Caffeic and ferulic acids, dissolved in saturated aqueous solutions at pH 3 or 7.2, have been tested for their capability to permeate through excised human skin mounted in Franz cells. At both pH values, ferulic and, at a lower degree, caffeic acids appeared able to permeate through the stratum corneum. The known higher lipophilicity of ferulic acid may explain the fact that it permeates through the stratum corneum better than caffeic acid. However, vehicle pH values proved to have no influence on biophenol skin permeation profile; this observed lack of pH effect may reflect the drug higher concentration attainable in saturated solutions at high pH. On the basis of the findings obtained in these in vitro experiments, we designed the schedule of a series of in vivo experiments, carried out to evaluate the ability of caffeic and ferulic acids to reduce, in healthy human volunteers, UVB-induced skin erythema, monitored by means of reflectance spectrophotometry. Caffeic and ferulic acids, dissolved in saturated aqueous solution pH 7.2, proved to afford a significant protection to the skin against UVB-induced erythema. To conclude, we have confirmed, by means of in vitro and in vivo experiments, that caffeic and ferulic acids may be successfully employed as topical protective agents against UV radiation-induced skin damage; however their skin absorption is not influenced by the pH of the formulation. © 2000 Elsevier Science B.V. All rights reserved. Keywords: Caffeic acid; Ferulic acid; Antioxidant; Skin permeation; Photooxidative damage www.elsevier.com/locate/ijpharm * Corresponding author. Tel.: +39-90-6766530; fax: +39- 90-3533142. E-mail address: saija@pharma.unime.it (A. Saija) 0378-5173/00/$ - see front matter © 2000 Elsevier Science B.V. All rights reserved. PII:S0378-5173(00)00358-6