Archives of Dermatological Research

, Volume 311, Issue 10, pp 773–793 | Cite as

Resveratrol-loaded nanoemulsion gel system to ameliorate UV-induced oxidative skin damage: from in vitro to in vivo investigation of antioxidant activity enhancement

  • Bijay Sharma
  • Babar Iqbal
  • Shobhit Kumar
  • Javed Ali
  • Sanjula BabootaEmail author
Original Paper


In the present study resveratrol nanoemulsion gel was developed and optimized with the aim of enhancing the permeability and antioxidant activity against ultraviolet (UV)-induced oxidative skin damage. Droplet size, polydispersity index, drug permeation flux, permeability coefficient and drug deposition in skin of resveratrol-loaded nanoemulsion were found to be 65.00 ± 5.00 nm, 0.171 ± 0.082, 144.50 μg/cm2/h, 2.90 × 10–2 cm/h and 45.65 ± 4.76%, respectively, whereas drug permeation flux, permeability coefficient and drug deposition in skin from nanoemulsion gel were found to be 107.70 μg/cm2/h, 2.06 × 10–2 cm/h and 62.65 ± 4.98%, respectively. Confocal studies depicted deeper penetration of resveratrol from nanoemulsion gel. Differential scanning calorimetry and Fourier-transform infrared spectrophotometer studies confirmed that nanoemulsion gel enhanced fluidization of stratum corneum lipids and conformational disruption of lipid bilayer, thereby enhancing skin permeation of resveratrol. Histopathology study of skin revealed that resveratrol-loaded nanoemulsion gel inhibited UV-induced spongosis, edema and epidermal hyperplasia response. Levels of glutathione, superoxide dismutase, catalase and protein carbonyl in the skin of UV-irradiated rats were significantly (p < 0.01) improved in the skin of animals treated with nanoemulsion gel. Experimental results suggested that nanoemulsion gel could be explored as a promising carrier for topical delivery of resveratrol for prevention of UV-induced oxidative skin damage owing to its enhanced permeability and retention effect.


Nanoemulsion Topical drug delivery Nanoemulsion gel Antioxidant Skin permeation 


Compliance with ethical standards

Conflict of interest

The authors report no conflicts of interest.


  1. 1.
    Schieber M, Chandel NS (2014) ROS function in redox signaling and oxidative stress. Curr Biol 24:R453–R462CrossRefGoogle Scholar
  2. 2.
    Kryston TB, Georgiev AB, Pissis P, Georgakilas AG (2011) Role of oxidative stress and DNA damage in human carcinogenesis. Mutat Res 711:193–201CrossRefGoogle Scholar
  3. 3.
    Sharma S, Narang JK, Ali J, Baboota S (2016) Synergistic antioxidant action of vitamin E and rutin SNEDDS in ameliorating oxidative stress in a Parkinson’s disease model. Nanotechnology 27:375101CrossRefGoogle Scholar
  4. 4.
    Choudhari SK, Chaudhary M, Gadbail AR, Sharma A, Tekade S (2014) Oxidative and antioxidative mechanisms in oral cancer and precancer: a review. Oral Oncol 50:10–18CrossRefGoogle Scholar
  5. 5.
    Darr D, Fridovich I (1994) Free radicals in cutaneous biology. J Investig Dermatol 102:671–675CrossRefGoogle Scholar
  6. 6.
    Kruk J, Duchnik E (2014) Oxidative stress and skin diseases: possible role of physical activity. Asian Pac J Cancer Prev 15:561–568CrossRefGoogle Scholar
  7. 7.
    Wiseman H, Halliwell B (1996) Damage to DNA by reactive oxygen and nitrogen species: role in inflammatory disease and progression to cancer. Biochem J 313:17–29CrossRefGoogle Scholar
  8. 8.
    Addor FAS (2017) Antioxidants in dermatology. An Bras Dermatol 92:356–362CrossRefGoogle Scholar
  9. 9.
    Ji H, Li XK (2016) Oxidative stress in atopic dermatitis. Oxidative Med Cell Longev 2016:1–8CrossRefGoogle Scholar
  10. 10.
    Baur JA, Sinclair DA (2006) Therapeutic potential of resveratrol: the in vivo evidence. Nat Rev Drug Discov 5:493–506CrossRefGoogle Scholar
  11. 11.
    Singh G, Pai RS (2014) Recent advances of resveratrol in nanostructured based delivery systems and in the management of HIV/AIDS. J Control Release 194:178–188CrossRefGoogle Scholar
  12. 12.
    Summerlin N, Soo E, Thakur S, Qu Z, Jambhrunkar S, Popat A (2015) Resveratrol nanoformulations: challenges and opportunities. Int J Pharm. CrossRefPubMedGoogle Scholar
  13. 13.
    Joraholmen MW, Skalko-Basnet N, Acharya G, Basnet P (2015) Resveratrol-loaded liposomes for topical treatment of the vaginal inflammation and infections. Eur J Pharm Sci 79:112–121CrossRefGoogle Scholar
  14. 14.
    Kim JH, Park EY, Ha HK, Jo CM, Lee WJ, Lee SS, Kim JW (2016) Resveratrol-loaded nanoparticles induce antioxidant activity against oxidative stress. Asian Australas J Anim Sci 29:288–298CrossRefGoogle Scholar
  15. 15.
    Pangeni R, Sharma S, Mustafa G, Ali J, Baboota S (2014) Vitamin E loaded resveratrol nanoemulsion for brain targeting for the treatment of Parkinson's disease by reducing oxidative stress. Nanotechnology 25:485102CrossRefGoogle Scholar
  16. 16.
    Park S, Cha SH, Cho I, Park S, Park Y, Cho S, Park Y (2016) Antibacterial nanocarriers of resveratrol with gold and silver nanoparticles. Mater Sci Eng C Mater Biol Appl 58:1160–1169CrossRefGoogle Scholar
  17. 17.
    Sessa M, Balestrieri ML, Ferrari G, Servillo L, Castaldo D, D'Onofrio N, Donsì F, Tsao R (2014) Bioavailability of encapsulated resveratrol into nanoemulsion-based delivery systems. Food Chem 147:42–50CrossRefGoogle Scholar
  18. 18.
    Vinardell MP, Mitjans M (2015) Nanocarriers for delivery of antioxidants on the skin. Cosmetics 2:342–354CrossRefGoogle Scholar
  19. 19.
    Teskac K, Kristl J (2010) The evidence for solid lipid nanoparticles mediated cell uptake of resveratrol. Int J Pharm 390:61–69CrossRefGoogle Scholar
  20. 20.
    Pando D, Caddeo C, Manconib M, Fadda AM, Pazos C (2013) Nanodesign of olein vesicles for the topical delivery of the antioxidant resveratrol. J Pharm Pharmacol 65:1158–1167CrossRefGoogle Scholar
  21. 21.
    Friedrich RB, Kann B, Coradini K, Offerhaus HL, Beck RC, Windbergs M (2015) Skin penetration behavior of lipid-core nanocapsules for simultaneous delivery of resveratrol and curcumin. Eur J Pharm Sci 78:204–213CrossRefGoogle Scholar
  22. 22.
    Immacolata S, DanielaDe S, Virginia C, Laura M, Rosa C, Gabriella F, Fabio A, Maria IR, GiuseppeDe R (2013) Nanocarriers for topical administration of resveratrol: a comparative study. Int J Pharm 440:179–187CrossRefGoogle Scholar
  23. 23.
    Kumar D, Ali J, Baboota S (2016) Omega 3 fatty acid-enriched nanoemulsion of thiocolchicoside for transdermal delivery: formulation, characterization and absorption studies. Drug Deliv 23:591–600CrossRefGoogle Scholar
  24. 24.
    Anton N, Vandamme TF (2011) Nano-emulsions and micro-emulsions: clarifications of the critical differences. Pharm Res 28:978–985CrossRefGoogle Scholar
  25. 25.
    Kumar S, Ali J, Baboota S (2016) Design Expert® supported optimization and predictive analysis of selegiline nanoemulsion via the olfactory region with enhanced behavioural performance in Parkinson’s disease. Nanotechnology 27:435101CrossRefGoogle Scholar
  26. 26.
    Shakeel F, Baboota S, Ahuja A, Ali J, Aqil M, Shafiq S (2007) Nanoemulsions as vehicles for transdermal delivery of aceclofenac. AAPS Pharmscitech 8:191–199CrossRefGoogle Scholar
  27. 27.
    Kumar A, Ahuja A, Ali J, Baboota S (2016) Curcumin-loaded lipid nanocarrier for improving bioavailability, stability and cytotoxicity against malignant glioma cells. Drug Deliv 23:214–229CrossRefGoogle Scholar
  28. 28.
    Sharma S, Sahni JK, Ali J, Baboota S (2015) Effect of high-pressure homogenization on formulation of TPGS loaded nanoemulsion of rutin—pharmacodynamic and antioxidant studies. Drug Deliv 22:541–551CrossRefGoogle Scholar
  29. 29.
    Shakeel F, Baboota S, Ahuja A, Ali J, Shafiq S (2008) Celecoxib nanoemulsion: skin permeation mechanism and bioavailability assessment. J Drug Target 16:733–740CrossRefGoogle Scholar
  30. 30.
    Barakat NS (2010) Evaluation of glycofurol-based gel as a new vehicle for topical application of naproxen. AAPS Pharmscitech 11:1138–1146CrossRefGoogle Scholar
  31. 31.
    Nguyen HX, Puri A, Banga AK (2017) Methods to simulate rubbing of topical formulation for in vitro skin permeation studies. Int J Pharm 519:22–33CrossRefGoogle Scholar
  32. 32.
    Iqbal B, Ali J, Baboota S (2018) Silymarin loaded nanostructured lipid carrier: from design and dermatokinetic study to mechanistic analysis of epidermal drug deposition enhancement. J Mol Liq 255:513-529. CrossRefGoogle Scholar
  33. 33.
    Ghate VM, Lewis SA, Prabhu P, Dubey A, Patel N (2016) Nanostructured lipid carriers for the topical delivery of tretinoin. Eur J Pharm Biopharm 108:253–261CrossRefGoogle Scholar
  34. 34.
    Han F, Yin R, Che X, Yuan J, Cui Y, Yin H, Li S (2012) Nanostructured lipid carriers (NLC) based topical gel of flurbiprofen: design, characterization and in vivo evaluation. Int J Pharm 439:349–357CrossRefGoogle Scholar
  35. 35.
    Pandey YR, Kumar S, Gupta BK, Ali J, Baboota S (2016) Intranasal delivery of paroxetine nanoemulsion via the olfactory region for the management of depression: formulation, behavioural and biochemical estimation. Nanotechnology 27:025102CrossRefGoogle Scholar
  36. 36.
    Wan T, Xu T, Pan J, Qin M, Pan W, Zhang G, Wu Z, Wu C, Xu Y (2015) Microemulsion based gel for topical dermal delivery of pseudolaric acid B: in vitro and in vivo evaluation. Int J Pharm 493:111–120CrossRefGoogle Scholar
  37. 37.
    Mayer S, Weiss J, McClements DJ (2013) Vitamin E-enriched nanoemulsions formed by emulsion phase inversion: factors influencing droplet size and stability. J Colloid Interface Sci 402:122–130CrossRefGoogle Scholar
  38. 38.
    Naz Z, Ahmad FJ (2015) Curcumin-loaded colloidal carrier system: formulation optimization, mechanistic insight, ex vivo and in vivo evaluation. Int J Nanomed 10:4293–4307CrossRefGoogle Scholar
  39. 39.
    Khurana S, Jain NK, Bedi PMS (2013) Nanoemulsion based gel for transdermal delivery of meloxicam: physico-chemical, mechanistic investigation. Life Sci 92:383–392CrossRefGoogle Scholar
  40. 40.
    Harwansh RK, Mukherjee PK, Bahadur S, Biswas R (2015) Enhanced permeability of ferulic acid loaded nanoemulsion based gel through skin against UVA mediated oxidative stress. Life Sci 141:202–211CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Bijay Sharma
    • 1
  • Babar Iqbal
    • 1
  • Shobhit Kumar
    • 2
  • Javed Ali
    • 3
  • Sanjula Baboota
    • 3
    Email author
  1. 1.Pharmaceutical Research Laboratory, Department of Pharmaceutics, School of Pharmaceutical Education and ResearchJamia Hamdard (Hamdard University)New DelhiIndia
  2. 2.Department of Pharmaceutical TechnologyMeerut Institute of Engineering and Technology (MIET)MeerutIndia
  3. 3.Department of Pharmaceutics, School of Pharmaceutical Education and ResearchJamia Hamdard (Hamdard University)New DelhiIndia

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