Delivery of Resveratrol, a Red Wine Polyphenol, from Solutions and Hydrogels <i>via</i> the Skin

Abstract

Resveratrol is a naturally occurring polyphenolic compound which has received much attention in the prevention of and therapy for cardiovascular diseases and cancers ( Fig. 1).1) Red grapes and wines contain considerable amounts of resveratrol. Resveratrol has many benefits for the skin. Topically applied resveratrol has been shown to possess strong antiproliferative and chemopreventive properties against skin carcinogenesis.2-4) Resveratrol affords substantial protection against skin damage from ultraviolet B (UVB) exposure. 5,6) Resveratrol shows antimicrobial activity against dermatophytes and herpes simplex virus. 7,8) Resveratrol can also be used in the dermocosmetic field because of its role as a phytoestrogen based on its ability to activate estrogen receptors. 9)The oral bioavailability of resveratrol is poor, leading to an irrelevant in vivo effect with oral administration compared to its powerful in vitro efficacy. 10) Resveratrol also has a short initial half-life (8-14 min) and is extensively metabolized in the body.11) Several phase I clinical trials are currently underway for oral resveratrol in humans at doses of as high as 7.5 g per day. This would require 2.7 kg of resveratrol a year at a current cost of ca. US$6800. Therefore it is becoming increasingly important to find ways to improve the bioavailability of and block the metabolism of resveratrol. Delivery of resveratrol via the skin is an attractive alternative to oral dosing for both topical and transdermal applications.No evidence currently exists in the literature to support the notion that a sufficient amount of resveratrol can be delivered to produce therapeutic benefits via a skin route. Designs of optimal formulations for resveratrol permeation via the skin are also lacking. The purposes of this study were to establish basic profiles of resveratrol permeability into and across the skin. The optimal pH and co-solvent of the vehicles for resveratrol were investigated for better permeation. The present study utilized Franz cells to explore the in vitro skin permeation of resveratrol. The drug amount retained within the skin reservoir was determined by in vitro and in vivo methods. Various skin membranes, including nude mouse skin, stratum corneum (SC)-stripped skin, delipidized skin, and cellulose membranes, were used as permeation barriers to elucidate the mechanisms and pathways. One particular problem common to drug delivery systems designed for use on the skin is the poor retention at the site of application. This problem can be resolved by incorporating bioadhesive hydrogels within the system. Hence, the ability of a series of hydrogel formulations to deliver topically applied resveratrol was examined. The permeability of piceatannol (Fig. 1), a resveratrol analogue with considerably higher activity, was also evaluated in this study. Resveratrol, the main active polyphenol in red wine, has been demonstrated to show benefits against skin disorders. The bioavailability of orally administered resveratrol is insufficient to permit high...

Protective effects of equol and their polyphenolic isomers against dermal aging: Microarray/protein evidence with clinical implications and unique delivery into human skin

“…While it should be pointed out that transcutol (as a skin penetrating vehicle) may form an intracutaneous depot for drugs used in topical formulations (Shokri et al, 2012), it is more likely that the applied equol is sequestered into the epidermal compartment due to the abundance of estrogen receptor subtypes in keratinocytes for which equol has a high affinity (Lephart, 2013a;Lund et al, 2011;Setchell et al, 2005;Thorton et al, 2003). This notion is supported by quantification of the [ 3 H]-equol in the epidermis where the content was higher than typically seen with most other compounds, such as other polyphenolic molecules like resveratrol, the isoflavonoid, genistein, or topical drugs like 17b-estradiol (Chadha et al, 2011;Hung et al, 2008;Xing et al, 2009;Zhong et al, 2009). The reservoir forming properties of equol in the epidermis may be due to its lipophilic characteristics where its octanol-water partition coefficient is 3.20, which is higher than other polyphenolic molecules (Rothwell et al, 2005).…”

Efficient Delivery and Distribution in Skin of Chlorogenic Acid and Resveratrol Induced by Microemulsion Using Sucrose Laurate

“…Second, the low viscosity of MESL could facilitate solute diffusion in the vehicle and access onto the skin surface. 23) This should improve the release of a solute from the vehicle and penetration into skin. Furthermore, some sucrose laurate in the microemulsion might penetrate into skin and interact directly with corneocytes or lipid components in the stratum corneum, 20,24) increasing fluidity, thereby enhancing skin incorporation and the diffusion of polyphenols.…”

Topical delivery of silymarin constituents via the skin route

“…The pH of the aqueous vehicle was shown to be one of the major variables that can infl uence the diffusivity of drugs [21,22] . The structures of silymarin constituents have multiple protonation sites.…”