NoteChlorogenic acid (Fig. 1), which is a well-known antioxidant, is an abundant ingredient in coffee and is also found in many foods, such as sweet potatoes and apples.1-3) It has been suggested that chlorogenic acid has anti-inflammatory and anticancer activities and is also effective to prevent cardiovascular disease [4][5][6] and to decrease blood glucose levels.7) Like other plant polyphenols, its application for topical purposes, such as photoprotection against UV-induced skin damage (photoaging), skin cancer prevention, and skin care, is expected. 8,9) Different from other plant polyphenols, such as resveratrol, quercetin, and genistein, chlorogenic acid is hydrophilic and soluble in water. For hydrophilic compounds, lipid lamella in the stratum corneum works as a barrier to their intradermal and transdermal delivery 10) ; therefore, to apply chlorogenic acid for topical purposes, it is necessary to improve interadermal delivery.Microemulsions consist of an aqueous phase, an organic phase, a surfactant and a co-surfactant component, which are thermodynamically stable and have been shown to have high solubilization capacity and to facilitate the skin permeation of both lipophilic and hydrophilic drugs. 11,12) In previous studies we have clarified that microemulsions, especially a water-in-oil (w/o type) microemulsion consisting of 150 mM NaCl solution, isopropyl myristate, polyoxyethylene sorbitan monooleate (Tween 80) and ethanol markedly increased the intradermal delivery as well as solubility of hydrophobic polyphenols quercetin and genistein, whose solubility in both aqueous and organic media is very low. 13,14) Although improvement of solubility does not usually lead to increased solute skin delivery, microemulsions effectively improved skin delivery of these polyphenols; therefore, microemulsions seemed to be useful as a vehicle for the skin delivery of solutes whose solubility in ordinal vehicles is limited. Different from quercetin and genistein, since chlorogenic acid is hydrophilic, moderate solubility in aqueous medium is expected, although for hydrophilic compounds permeation through stratum corneum lipid lamella is a big problem for their skin delivery. In this study we first examined the intradermal delivery of chlorogenic acid from aqueous medium. We also examined the effects of w/o-type and an oil-in water (o/w-type) microemulsions on its delivery. We furthermore examined the effects of the topical application of chlorogenic acid in vivo using guinea pigs on ultraviolet light-induced erythema formation in the presence and absence of microemulsion gel, in which co-surfactant ethanol concentration was minimized to avoid skin damage by alcohol.
Results and DiscussionWe first examined the solubility of chlorogenic acid. As shown in Fig. 2, the solubility of chlorogenic acid in 150 mM NaCl solution was about 43 mM, which was much greater than the values of other polyphenols revealed previously, such as quercetin (0.31 mM) 13) and genistein (0.059 mM).
14)We examined the effects of three microemu...