AAPS PharmSciTech

, Volume 16, Issue 2, pp 364–374 | Cite as

Development and Evaluation of Curcumin-loaded Elastic Vesicles as an Effective Topical Anti-inflammatory Formulation

  • Rumjhum Agrawal
  • Simarjot Kaur Sandhu
  • Ikksheta Sharma
  • Indu Pal Kaur
Research Article


Curcumin has diverse biological activities including antioxidant and anti-inflammatory activity. However, its clinical use for topical application is limited due to its poor aqueous solubility and thus, minimal cutaneous bioavailability. Elastic vesicles (EVs) of curcumin were prepared to improve its cutaneous bioavailability and to use it for topical anti-inflammatory effect. Ex vivo skin permeation and retention studies were performed to check if incorporation of curcumin into EVs could improve its permeation into and retention in the skin. Evaluation of acute and chronic anti-inflammatory effect was done using xylene-induced acute ear edema in mice and cotton pellet-induced chronic inflammation in rats, respectively. A significant improvement in flux (nine times) across murine skin was observed when aqueous dispersion of curcumin (flux − 0.46 ± 0.02 μg/h/cm2) was compared with curcumin-loaded EVs (flux − 4.14 ± 0.04 μg/h/cm2 ). Incorporation of these curcumin-loaded EVs into a hydrophilic ointment base resulted in higher skin retention (51.66%) in contrast to free curcumin ointment (1.64%) and a marketed formulation (VICCO® turmeric skin cream). The developed ointment showed an effect similar (p < 0.05) to the marketed diclofenac sodium ointment (Omni-gel®) in suppression of acute inflammation in mouse; a significant inhibition (28.8% versus 3.91% for free curcumin) of cotton pellet-induced chronic inflammation was also observed. Thus, curcumin-loaded EVs incorporated in hydrophilic ointment is a promising topical anti-inflammatory formulation.


anti-inflammatory curcumin elastic vesicles topical formulation 


  1. 1.
    Duvoix A, Blasius R, Delhalle S, Schnekenburger M, Morceau F, Henry E, et al. Chemopreventive and therapeutic effects of curcumin. Cancer Lett. 2005;223(2):181–90.CrossRefPubMedGoogle Scholar
  2. 2.
    Hsuuw YD, Chang CK, Chan WH, Yu JS. Curcumin prevents methylglyoxal-induced oxidative stress and apoptosis in mouse embryonic stem cells and blastocysts. J Cell Physiol. 2005;205(3):379–86.CrossRefPubMedGoogle Scholar
  3. 3.
    Aggarwal BB, Kumar A, Bharti AC. Anticancer potential of curcumin: preclinical and clinical studies. Anticancer Res. 2003;23(1A):363–98.PubMedGoogle Scholar
  4. 4.
    Sun J, Zhao Y, Hu J. Curcumin inhibits imiquimod-induced psoriasis-like inflammation by inhibiting IL-1beta and IL-6 production in mice. PLoS One. 2013;8(6):e67078.CrossRefPubMedCentralPubMedGoogle Scholar
  5. 5.
    Menon VP, Sudheer AR. Antioxidant and anti-inflammatory properties of curcumin. Adv Exp Med Biol. 2007;595:105–25.CrossRefPubMedGoogle Scholar
  6. 6.
    Deng S-L, Chen W-F, Zhou B, Yang L, Liu Z-L. Protective effects of curcumin and its analogues against free radical-induced oxidative haemolysis of human red blood cells. Food Chem. 2006;98(1):112–9.CrossRefGoogle Scholar
  7. 7.
    Osawa T, Kato Y. Protective role of antioxidative food factors in oxidative stress caused by hyperglycemia. Ann N Y Acad Sci. 2005;1043:440–51.CrossRefPubMedGoogle Scholar
  8. 8.
    Strasser EM, Wessner B, Manhart N, Roth E. The relationship between the anti-inflammatory effects of curcumin and cellular glutathione content in myelomonocytic cells. Biochem Pharmacol. 2005;70(4):552–9.CrossRefPubMedGoogle Scholar
  9. 9.
    Kakkar V, Singh S, Singla D, Kaur IP. Exploring solid lipid nanoparticles to enhance the oral bioavailability of curcumin. Mol Nutr Food Res. 2010;55(3):495–503.CrossRefPubMedGoogle Scholar
  10. 10.
    Kaur IP, Kapila M, Agrawal R. Role of novel delivery systems in developing topical antioxidants as therapeutics to combat photoageing. Ageing Res Rev. 2007;6(4):271–88.CrossRefPubMedGoogle Scholar
  11. 11.
    Bansal SS, Goel M, Aqil F, Vadhanam MV, Gupta RC. Advanced drug delivery systems of curcumin for cancer chemoprevention. Cancer Prev Res (Phila). 2011;4(8):1158–71.CrossRefGoogle Scholar
  12. 12.
    Kakkar V, Kaur IP. Evaluating potential of curcumin loaded solid lipid nanoparticles in aluminium induced behavioural, biochemical and histopathological alterations in mice brain. Food Chem Toxicol. 2011;49(11):2906–13.CrossRefPubMedGoogle Scholar
  13. 13.
    Bhushan S, Kakkar V, Pal HC, Guru SK, Kumar A, Mondhe DM, et al. Enhanced anticancer potential of encapsulated solid lipid nanoparticles of TPD: a novel triterpenediol from Boswellia serrata. Mol Pharm. 2012;10(1):225–35.CrossRefPubMedGoogle Scholar
  14. 14.
    Chen Y, Wu Q, Zhang Z, Yuan L, Liu X, Zhou L. Preparation of curcumin-loaded liposomes and evaluation of their skin permeation and pharmacodynamics. Molecules. 2012;17(5):5972–87.CrossRefPubMedGoogle Scholar
  15. 15.
    Zhao YZ, Lu CT, Zhang Y, Xiao J, Zhao YP, Tian JL, et al. Selection of high efficient transdermal lipid vesicle for curcumin skin delivery. Int J Pharm. 2013;454(1):302–9.CrossRefPubMedGoogle Scholar
  16. 16.
    Gallarate M, Chirio D, Trotta M, Eugenia Carlotti M. Deformable liposomes as topical formulations containing alpha-tocopherol. J Dispers Sci Technol. 2006;27(5):703–13.CrossRefGoogle Scholar
  17. 17.
    Castangia I, Nacher A, Caddeo C, Valenti D, Fadda AM, Diez-Sales O, et al. Fabrication of quercetin and curcumin bionanovesicles for the prevention and rapid regeneration of full-thickness skin defects on mice. Acta Biomater. 2013;10(3):1292–300.CrossRefPubMedGoogle Scholar
  18. 18.
    Chaudhary H, Kohli K, Kumar V. Nano-transfersomes as a novel carrier for transdermal delivery. Int J Pharm. 2013;454(1):367–80.CrossRefPubMedGoogle Scholar
  19. 19.
    Naksuriya O, Okonogi S, Schiffelers RM, Hennink WE. Curcumin nanoformulations: a review of pharmaceutical properties and preclinical studies and clinical data related to cancer treatment. Biomaterials. 2014;35(10):3365–83.CrossRefPubMedGoogle Scholar
  20. 20.
    Agrawal R, Kaur IP. Inhibitory effect of encapsulated curcumin on ultraviolet-induced photoaging in mice. Rejuvenation Res. 2010;13(4):397–410.CrossRefPubMedGoogle Scholar
  21. 21.
    Cevc G, Blume G, Schätzlein A. Transfersomes-mediated transepidermal delivery improves the regio-specificity and biological activity of corticosteroids in vivo. J Control Release. 1997;45(3):211–26.CrossRefGoogle Scholar
  22. 22.
    El Maghraby GM, Williams AC, Barry BW. Skin hydration and possible shunt route penetration in controlled estradiol delivery from ultradeformable and standard liposomes. J Pharm Pharmacol. 2001;53(10):1311–22.CrossRefPubMedGoogle Scholar
  23. 23.
    El Maghraby GMM, Williams AC, Barry BW. Interactions of surfactants (edge activators) and skin penetration enhancers with liposomes. Int J Pharm. 2004;276:143–61.CrossRefPubMedGoogle Scholar
  24. 24.
    Essa EA, Bonner MC, Barry BW. Iontophoretic estradiol skin delivery and tritium exchange in ultradeformable liposomes. Int J Pharm. 2002;240(1–2):55–66.CrossRefPubMedGoogle Scholar
  25. 25.
    Ma Y, Li Y, Li X, Wu Y. Anti-inflammatory effects of 4-methylcyclopentadecanone on edema models in mice. Int J Mol Sci. 2013;14(12):23980–92.CrossRefPubMedCentralPubMedGoogle Scholar
  26. 26.
    Niu X, Li Y, Li W, Hu H, Yao H, Li H, et al. The anti-inflammatory effects of Caragana tangutica ethyl acetate extract. J Ethnopharmacol. 2014;152(1):99–105.CrossRefPubMedGoogle Scholar
  27. 27.
    Swingle KF, Shideman FE. Phases of the inflammatory response to subcutaneous implantation of a cotton pellet and their modification by certain anti-inflammatory agents. J Pharmacol Exp Ther. 1972;183(1):226–34.PubMedGoogle Scholar
  28. 28.
    Fabri RL, Garcia RA, Florencio JR, de Castro Campos Pinto N, de Oliveira LG, Aguiar JA, et al. Anti-inflammatory and antioxidative effects of the methanolic extract of the aerial parts of Mitracarpus frigidus in established animal models. J Pharm Pharmacol. 2013;66(5):722–33.Google Scholar
  29. 29.
    Ntimenou V, Fahr A, Antimisiaris SG. Elastic vesicles for transdermal drug delivery of hydrophilic drugs: a comparison of important physicochemical characteristics of different vesicle types. J Biomed Nanotechnol. 2012;8(4):613–23.CrossRefPubMedGoogle Scholar
  30. 30.
    Uchino T, Lefeber F, Gooris G, Bouwstra J. Physicochemical characterization of drug-loaded rigid and elastic vesicles. Int J Pharm. 2011;412(1–2):142–7.CrossRefPubMedGoogle Scholar
  31. 31.
    van den Bergh BA, Wertz PW, Junginger HE, Bouwstra JA. Elasticity of vesicles assessed by electron spin resonance, electron microscopy and extrusion measurements. Int J Pharm. 2001;217(1–2):13–24.CrossRefPubMedGoogle Scholar
  32. 32.
    Setthacheewakul S, Mahattanadul S, Phadoongsombut N, Pichayakorn W, Wiwattanapatapee R. Development and evaluation of self-microemulsifying liquid and pellet formulations of curcumin, and absorption studies in rats. Eur J Pharm Biopharm. 2010;76:475–85.CrossRefPubMedGoogle Scholar
  33. 33.
    Bronaugh RL, Stewart RF. Methods for in vitro percutaneous absorption studies. VI: preparation of the barrier layer. J Pharm Sci. 1986;75(5):487–91.CrossRefPubMedGoogle Scholar
  34. 34.
    Catz P, Friend DR. Transdermal delivery of levonorgestrel. VIII. Effect of enhancers on rat skin, hairless mouse skin, hairless guinea pig skin, and human skin. Int J Pharm. 1990;58(2):93–102.CrossRefGoogle Scholar
  35. 35.
    Bronaugh RL, Stewart RF. Methods for in vitro percutaneous absorption studies III: hydrophobic compounds. J Pharm Sci. 1984;73(9):1255–8.CrossRefPubMedGoogle Scholar
  36. 36.
    Cevc G, Gebauer D, Stieber J, Schatzlein A, Blume G. Ultraflexible vesicles, Transfersomes, have an extremely low pore penetration resistance and transport therapeutic amounts of insulin across the intact mammalian skin. Biochim Biophys Acta. 1998;1368(2):201–15.CrossRefPubMedGoogle Scholar
  37. 37.
    Jain S, Jain P, Umamaheshwari RB, Jain NK. Transfersomes—a novel vesicular carrier for enhanced transdermal delivery: development, characterization, and performance evaluation. Drug Dev Ind Pharm. 2003;29(9):1013–26.CrossRefPubMedGoogle Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2014

Authors and Affiliations

  • Rumjhum Agrawal
    • 1
  • Simarjot Kaur Sandhu
    • 1
  • Ikksheta Sharma
    • 1
  • Indu Pal Kaur
    • 1
  1. 1.Department of PharmaceuticsUniversity Institute of Pharmaceutical Sciences, Panjab UniversityChandigarhIndia

Personalised recommendations