Trans-resveratrol (RES) and N-acetylcysteine (NAC) have protective effects on biological processes; therefore, they are frequently included in food supplements. Their possible applications for the prevention of free radical-induced damage to the skin are of particular physiological relevance; however, their usefulness is limited by their metabolic fate and the unpredictability of their delivery to the skin following oral administration. In this work, we evaluated the concomitant and direct application of RES and NAC on the skin using a self-nanoemulsifying system we previously developed for the oral delivery of poorly absorbed food supplements. We evaluated the capability of this system to increase RES and NAC accumulation in porcine skin using permeation studies in Franz diffusion cells. The ascorbyl palmitate (ASP) self-nanoemulsifying system considerably increased RES and NAC accumulation in the epidermis and dermis, which peaked 6 h after application. This study reveals a new formulation strategy to improve the bioavailability of ingredients, which was previously used in the health supplements field, but has rarely been employed in dermatology because of its poor distribution in the skin.
AfaqF, KatiyarSK. (2011) Polyphenols: skin photoprotection and inhibition of photocarcinogenesis. Mini Review in Medicinal Chemistry, 11, 1200–1215.
2.
ElmetsCA, LedetJJ, AtharM. (2014) Cyclooxygenases: mediators of UV-induced skin cancer and potential targets for prevention. Journal of Investigative Dermatology, 134, 2497–2502.
3.
RogersHW, WeinstockMA, HarrisAR, HinckleyMR, FeldmanSR, FleisherAB, ColdironBM. (2010) Incidence estimate of nonmelanoma skin cancer in the United States, 2006. Archives of Dermatology, 146, 283–287.
4.
RijnkelsJM, MoisonRM, PoddaE, van HenegouwenGM. (2003) Photoprotection by antioxidants against UVB-radiation-induced damage in pig skin organ culture. Radiation Research, 159, 210–217.
5.
BaldisserottoA, VertuaniS, BinoA, De LuciaD, LamprontiI, MilaniR, GambariR, ManfrediniS. (2015) Design, synthesis and biological activity of a novel Rutin analogue with improved lipid soluble properties. Bioorganic & Medicinal Chemistry, 23, 264–271.
6.
CatalgolB, BatirelS, TagaY, OzerNK. (2012) Resveratrol: French paradox revisited. Frontiers in Pharmacology, 3, 141.
7.
PirolaL, FröjdöS. (2008) Resveratrol: one molecule, many targets. IUBMB Life, 60, 323–332.
8.
LiY, CaoZ, ZhuH. (2006) Upregulation of endogenous antioxidants and phase 2 enzymes by the red wine polyphenol, resveratrol in cultured aortic smooth muscle cells leads to cytoprotection against oxidative and electrophilic stress. Pharmacological Research, 53, 6–15.
9.
PettiS, ScullyC. (2009) Polyphenols, oral health and disease: A review. Journal of Dentistry, 37, 413–423.
10.
RobertsMS, PughWJ, HadgraftJ. (1996) Epidermal permeability: penetrant structure relationships. 2. The effect of H-bonding groups in penetrants on their diffusion through the stratum corneum. International Journal of Pharmaceutics, 132, 23–42.
11.
HungCF, LinYK, HuangZR, FangJY. (2008) Delivery of resveratrol, a red wine polyphenol, from solutions and hydrogels via the skin. Biological & Pharmaceutical Bulletin, 31, 955–962.
12.
LopesLB. (2014) Overcoming the cutaneous barrier with Microemulsions. Pharmaceutics, 6, 52–77.
13.
de AlmeidaPA, AlvesMC, PoloniniHC, CalixtoSL, Braga GomesTB, Barros LatalizaAA, da Silveira RamosCD, Barbosa RaposoNR, de Oliveira FerreiraA, Fernandes BrandãoA. (2015) Studies with emulsion containing trans-resveratrol: in vitro release profile and ex vivo human skin permeation. Current Drug Delivery, 12, 157–165.
14.
SamuniY, GoldsteinS, DeanOM, BerkM. (2013) The chemistry and biological activities of N-acetylcysteine. Biochimica et Biophysica Acta, 1830, 4117–4129.
15.
AldavoodSJ, BehyarR, SarchahiAA, RadMA, NoroozianI, GhamsariSM, Sadeghi-HashjinG. (2003) Effect of acetylcysteine on experimental corneal wounds in dogs. Ophthalmic Research, 35, 319–323.
16.
MontesLF, WilbornWH, MontesCM. (2012) Topical acne treatment with acetylcysteine: clinical and experimental effects. Skinmed, 10, 348–351.
17.
BassottiA, MorenoS, CriadoE. (2011) Successful treatment with topical N-acetylcysteine in urea in five children with congenital lamellar ichthyosis. Pediatric Dermatology, 28, 451–455.
18.
Orihuela-CamposRC, TamakiN, MukaiR, FukuiM, MikiK, TeraoJ, ItoHO. (2015) Biological impacts of resveratrol, quercetin and N-acetylcisteine on oxidative stress in human gingival fibroblasts. Journal of Clinical Biochemistry and Nutrition, 56, 220–227.
19.
ScognamiglioI, De StefanoD, CampaniV, MayolL, CarnuccioR, FabbrociniG, AyalaF, La RotondaMI, De RosaG. (2013) Nanocarriers for topical administration of resveratrol: A comparative study. International Journal of Pharmaceutics, 440, 179–187.
20.
PoloniniHC, de Almeida BastosC, de OliveiraMAL, da SilvaCG, CollinsCH, BrandãoMA, RaposoNR. (2014) In vitro release and ex vivo percutaneous absorption of resveratrol cream using HPLC zirconized silica stationary phase. Journal of Chromatography. B, Analytical technologies in the biomedical and life sciences, 947-948, 23–31.
21.
GehmBD, McAndrewsJM, ChienPY, JamesonJL. (1997) Resveratrol, a polyphenolic compound found in grapes and wine, is an agonist for the estrogen receptor. Proceedings of the National Academy of Sciences of the USA, 94, 14138–14143.
22.
SunithaK, SureshP, SanthoshMS, HemshekharM, ThusharaRM, MaratheGK, ThirunavukkarasuC, KemparajuK, KumarMS, GirishKS. (2013) Inhibition of hyaluronidase by N-acetylcysteine and glutathione: role of thiol group in hyaluronan protection. International Journal of Biological Macromolecules, 55, 39–46.
23.
ChungJH, SeoJY, LeeMK, EunHC, LeeJH, KangS, FisherGJ, VoorheesJJ. (2002) Ultraviolet modulation of human macrophage metalloelastase in human skin in vivo. Journal of Investigative Dermatology, 119, 507–512.
24.
BartekMJ, LabuddeJA, MaibachHI. (1972) Skin permeability in vivo: comparison in rat, rabbit, pig and man. Journal of Investigative Dermatology, 58, 114–123.
25.
ZillichOV, Schweiggert-WeiszU, HasenkopfK, EisnerP, KerscherM. (2013) Antioxidant activity, lipophilicity and extractability of polyphenols from pig skin - development of analytical methods for skin permeation studies. Biomedical Chromatography, 27, 1444–1451.