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Novel nanoemulsion gel containing triple natural bio-actives combination of curcumin, thymoquinone, and resveratrol improves psoriasis therapy: in vitro and in vivo studies

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Abstract

Curcumin, resveratrol, and thymoquinone are the potential natural bio-actives reported with good anti-psoriatic activity. However, poor aqueous solubility and limited skin permeation of these natural bio-actives hinder their effective delivery and potential therapeutic outcome. In this regard, current research work focuses on the design and optimization of nanoemulsion (NE) gel formulation for the concurrent delivery of these three drugs. The NE system is consisting of oleic acid as oil phase, Tween 20 as surfactant, and PEG 200 as co-surfactant. The optimized formulation exhibited the droplet size 76.20 ± 1.67 nm, PDI of 0.12 ± 0.05, RI of 1.403 ± 0.007, and viscosity of 137.9 ± 4.07 mp. Carbopol 940 (0.5% w/v) was used as the gelling agent to prepare the NE gel which exhibited a good texture profile. The optimized formulation exhibited a higher % of growth inhibition on A-431 cells and demonstrated good anti-angiogenic activity in the HET-CAM test. Finally, in vivo studies in Balb/c mice model showed improved anti-psoriatic conditions which indicated that the triple natural bio-actives combination in nanoemulgel formulation is effective in the management of psoriasis.

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References

  1. Menter A, Korman NJ, Elmets CA, Feldman SR, Gelfand JM, Gordon KB, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis: section 3. Guidelines of care for the management and treatment of psoriasis with topical therapies. J Am Acad Dermatol. 2009;60:643–59.

    Article  PubMed  Google Scholar 

  2. Abdelbary AA, AbouGhaly MH. Design and optimization of topical methotrexate loaded niosomes for enhanced management of psoriasis: application of Box–Behnken design, in-vitro evaluation and in-vivo skin deposition study. Int J Pharm. 2015;485:235–43.

    Article  CAS  PubMed  Google Scholar 

  3. Raychaudhuri SK, Maverakis E, Raychaudhuri SP. Diagnosis and classification of psoriasis. Autoimmun Rev. 2014;13:490–5.

    Article  PubMed  Google Scholar 

  4. Bailey EE, Ference EH, Alikhan A, Hession MT, Armstrong AW. Combination treatments for psoriasis: a systematic review and meta-analysis. Arch Dermatol. 2012;148:511–22.

    Article  CAS  PubMed  Google Scholar 

  5. Kaur A, Katiyar SS, Kushwah V, Jain S. Nanoemulsion loaded gel for topical co-delivery of clobitasol propionate and calcipotriol in psoriasis. Nanomedicine. 2017;13:1473–82.

    Article  CAS  PubMed  Google Scholar 

  6. Badıllı U, Şen T, Tarımcı N. Microparticulate based topical delivery system of clobetasol propionate. AAPS PharmSciTech. 2011;12:949–57.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  7. Ali A, Ali S, Aqil M, Imam SS, Ahad A, Khan AQ. Thymoquinone loaded dermal lipid nano particles: Box Behnken design optimization to preclinical psoriasis assessment. J Drug Delivery Sci Technol. 2019;52:713–21.

    Article  CAS  Google Scholar 

  8. Akhtar M, Imam SS, Afroz Ahmad M, Najmi AK, Mujeeb M, Aqil M. Neuroprotective study of Nigella sativa-loaded oral provesicular lipid formulation: in vitro and ex vivo study. Drug Deliv. 2014;21:487–94.

    Article  CAS  PubMed  Google Scholar 

  9. Babazadeh B, Sadeghnia HR, Kapurchal ES, Parsaee H, Nasri S, Tayarani-Najaran Z. Protective effect of Nigella sativa and thymoquinone on serum/glucose deprivation-induced DNA damage in PC12 cells. Avicenna J Phytomed. 2012;2:125.

    PubMed  PubMed Central  Google Scholar 

  10. Sayeed S, Imam SS, Najmi AK, Aqil M, Akhtar M. Nonionic surfactant based thymoquinone loaded nanoproniosomal formulation: in vitro physicochemical evaluation and in vivo hepatoprotective efficacy. Drug Dev Ind Pharm. 2017;43:1413–20.

    Article  CAS  PubMed  Google Scholar 

  11. Jain A, Pooladanda V, Bulbake U, Doppalapudi S, Rafeeqi TA, Godugu C, et al. Liposphere mediated topical delivery of thymoquinone in the treatment of psoriasis. Nanomedicine. 2017;13:2251–62.

    Article  CAS  PubMed  Google Scholar 

  12. Löbenberg R, Amidon GL. Modern bioavailability, bioequivalence and biopharmaceutics classification system. New scientific approaches to international regulatory standards. Eur J Pharm Biopharm. 2000;50:3–12.

    Article  PubMed  Google Scholar 

  13. Kjær TN, Thorsen K, Jessen N, Stenderup K, Pedersen SB. Resveratrol ameliorates imiquimod-induced psoriasis-like skin inflammation in mice. PLoS One. 2015;10:e0126599.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  14. Shehzad A, Wahid F, Lee YS. Curcumin in cancer chemoprevention: molecular targets, pharmacokinetics, bioavailability, and clinical trials. Arch Pharm. 2010;343:489–99.

    Article  CAS  Google Scholar 

  15. Barygina V, Becatti M, Soldi G, Prignano F, Lotti T, Nassi P, et al. Altered redox status in the blood of psoriatic patients: involvement of NADPH oxidase and role of anti-TNF-α therapy. Redox Rep. 2013;18:100–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Di Nardo V, Gianfaldoni S, Tchernev G, Wollina U, Barygina V, Lotti J, et al. Use of curcumin in psoriasis. Open Access Maced J Med Sci. 2018;6:218–20.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Pradhan M, Singh D, Singh MR. Novel colloidal carriers for psoriasis: current issues, mechanistic insight and novel delivery approaches. J Control Release. 2013;170:380–95.

    Article  CAS  PubMed  Google Scholar 

  18. Acharya U, Rajarajan S, Acharya R, Acharya R, Chaudhary G, Ghimire S. Formulation, and evaluation of nanoemulsion based system for transdermal delivery of the antipsoriatic drug. World J Pharm Pharm Sci. 2017;6:732–48.

    CAS  Google Scholar 

  19. Mou D, Chen H, Du D, Mao C, Wan J, Xu H, et al. Hydrogel-thickened nanoemulsion system for topical delivery of lipophilic drugs. Int J Pharm. 2008;353:270–6.

    Article  CAS  PubMed  Google Scholar 

  20. Shaikh GH. Alternative medicine for psoriasis–natural herbal ayurvedic treatment—a review. J Curr Res Ayurvedic Pharm Sci. 2012;3.

  21. Mahtab A, Anwar M, Mallick N, Naz Z, Jain GK, Ahmad FJ. Transungual delivery of ketoconazole nanoemulgel for the effective management of onychomycosis. AAPS PharmSciTech. 2016;17:1477–90.

    Article  CAS  PubMed  Google Scholar 

  22. Akhter S, Jain GK, Ahmad FJ, Khar RK, Jain N, Khan ZI, et al. Investigation of nanoemulsion system for transdermal delivery of domperidone: ex-vivo and in vivo studies. Curr Nanosci. 2008;4:381–90.

    Article  CAS  Google Scholar 

  23. Haider MF, Khan S, Gaba B, Alam T, Baboota S, Ali J, et al. Optimization of rivastigmine nanoemulsion for enhanced brain delivery: in-vivo and toxicity evaluation. J Mol Liq. 2018;255:384–96.

    Article  CAS  Google Scholar 

  24. Azeem A, Rizwan M, Ahmad FJ, Iqbal Z, Khar RK, Aqil M, et al. Nanoemulsion components screening and selection: a technical note. AAPS PharmSciTech. 2009;10:69–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Gaba B, Khan T, Haider MF, Alam T, Baboota S, Parvez S, et al. Vitamin E loaded naringenin nanoemulsion via intranasal delivery for the management of oxidative stress in a 6-OHDA Parkinson’s disease model. Biomed Res Int. 2019;2019:1–20.

    Article  CAS  Google Scholar 

  26. Khatoon K, Rizwanullah M, Amin S, Mir SR, Akhter S. Cilnidipine loaded transfersomes for transdermal application: formulation optimization, in-vitro and in-vivo study. J Drug Delivery Sci Technol. Elsevier. 2019;54:101303.

    Article  CAS  Google Scholar 

  27. Sahu S, Katiyar SS, Kushwah V, Jain S. Active natural oil-based nanoemulsion containing tacrolimus for synergistic antipsoriatic efficacy. Nanomedicine. 2018;13:1985–98.

    Article  CAS  PubMed  Google Scholar 

  28. Baboota S, Alam MS, Sharma S, Sahni JK, Kumar A, Ali J. Nanocarrier-based hydrogel of betamethasone dipropionate and salicylic acid for treatment of psoriasis. Int J Pharm Investig. 2011;1:139–47.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. de Vargas BA, Bidone J, Oliveira LK, Koester LS, Bassani VL, Teixeira HF. Development of topical hydrogels containing genistein-loaded nanoemulsions. J Biomed Nanotechnol. American Scientific Publishers. 2012;8:330–6.

    Article  PubMed  CAS  Google Scholar 

  30. Hussain A, Samad A, Nazish I, Ahmed FJ. Nanocarrier-based topical drug delivery for an antifungal drug. Drug Dev Ind Pharm. 2014;40:527–41.

    Article  CAS  PubMed  Google Scholar 

  31. Kota K, Sharma S, Ragavendhra P. Study of antiangiogenic activity of “aqueous extract of Nigella sativa seeds” in chick chorioallantoic membrane (CAM) model. Int J Adv Med. 2018;5:895.

    Article  Google Scholar 

  32. 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:e67078.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Draize JH. Methods for the study of irritation and toxicity of substances applied topically to the skin and mucous membranes. J Pharmacol Exp Ther. 1944;82:377–90.

    CAS  Google Scholar 

  34. Touitou E, Godin B, Karl Y, Bujanover S, Becker Y. Oleic acid, a skin penetration enhancer, affects Langerhans cells and corneocytes. J Control Release. 2002;80:1–7.

    Article  CAS  PubMed  Google Scholar 

  35. Sood S, Jain K, Gowthamarajan K. Optimization of curcumin nanoemulsion for intranasal delivery using design of experiment and its toxicity assessment. Colloids Surf B: Biointerfaces. 2014;113:330–7.

    Article  CAS  PubMed  Google Scholar 

  36. El Maghraby GM. Transdermal delivery of hydrocortisone from eucalyptus oil microemulsion: effects of cosurfactants. Int J Pharm. 2008;355:285–92.

    Article  PubMed  CAS  Google Scholar 

  37. Anarjan N, Tan C. Effects of selected polysorbate and sucrose ester emulsifiers on the physicochemical properties of astaxanthin nanodispersions. Molecules. 2013;18:768–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Heuschkel S, Goebel A, Neubert RH. Microemulsions—modern colloidal carrier for dermal and transdermal drug delivery. J Pharm Sci. 2008;97:603–31.

    Article  CAS  PubMed  Google Scholar 

  39. Ahmed S, Gull A, Alam M, Aqil M, Sultana Y. Ultrasonically tailored, chemically engineered and “QbD” enabled fabrication of agomelatine nanoemulsion; optimization, characterization, ex-vivo permeation and stability study. Ultrason Sonochem. 2018;41:213–26.

    Article  CAS  PubMed  Google Scholar 

  40. Wennerström H, Olsson U. Microemulsions as model systems. C R Chim. 2009;12:4–17.

    Article  CAS  Google Scholar 

  41. Lawrence MJ, Rees GD. Microemulsion-based media as novel drug delivery systems. Adv Drug Deliv Rev. 2000;45:89–121.

    Article  CAS  PubMed  Google Scholar 

  42. Baboota S, Shakeel F, Ahuja A, Ali J, Shafiq S. Design, development and evaluation of novel nanoemulsion formulations for transdermal potential of celecoxib. Acta Pharma. 2007;57:315–32.

    Article  CAS  Google Scholar 

  43. Belhaj N, Dupuis F, Arab-Tehrany E, Denis FM, Paris C, Lartaud I, et al. Formulation, characterization and pharmacokinetic studies of coenzyme Q10 PUFA’s nanoemulsions. Eur J Pharm Sci. 2012;47:305–12.

    Article  CAS  PubMed  Google Scholar 

  44. Tuğcu-Demiröz F. Vaginal delivery of benzydamine hydrochloride through liposomes dispersed in mucoadhesive gels. Chem Pharm Bull. The Pharmaceutical Society of Japan. 2017:c17–00133.

  45. Jose A, Labala S, Ninave KM, Gade SK, Venuganti VVK. Effective skin cancer treatment by topical co-delivery of curcumin and STAT3 siRNA using cationic liposomes. AAPS PharmSciTech. 2018;19:166–75.

    Article  CAS  PubMed  Google Scholar 

  46. Zhai X, Ding J, Tang Z, Li J, Li Y, Yan Y, et al. Effects of resveratrol on the proliferation, apoptosis and telomerase ability of human A431 epidermoid carcinoma cells. Oncol Lett. Spandidos Publications. 2016;11:3015–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Park JE, Kim D-H, Ha E, Choi SM, Choi J-S, Chun K-S, et al. Thymoquinone induces apoptosis of human epidermoid carcinoma A431 cells through ROS-mediated suppression of STAT3. Chem Biol Interact. Elsevier. 2019;312:108799.

    Article  CAS  PubMed  Google Scholar 

  48. Agarwal S, Srivastava R, Mishra N. An overview of therapeutic potential of thymoquinone. Int J Pharm Sci Res. 2019;10(8):3532–3539.

  49. Gambini J, Inglés M, Olaso G, Lopez-Grueso R, Bonet-Costa V, Gimeno-Mallench L, et al. Properties of resveratrol: in vitro and in vivo studies about metabolism, bioavailability, and biological effects in animal models and humans. Oxidative Med Cell Longev. Hindawi. 2015:2015.

  50. Priyadarsini KI. The chemistry of curcumin: from extraction to therapeutic agent. Molecules. Multidisciplinary Digital Publishing Institute. 2014;19:20091–112.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  51. Alvarez-Román R, Naik A, Kalia Y, Guy RH, Fessi H. Skin penetration and distribution of polymeric nanoparticles. J Control Release. 2004;99:53–62.

    Article  PubMed  CAS  Google Scholar 

  52. Sankar L, Arumugam D, Sudha Boj PP. Expression of angiogenic factors in psoriasis vulgaris. J Clin Diagn Res. JCDR Research & Publications Private Limited. 2017;11:EC23.

    CAS  PubMed  PubMed Central  Google Scholar 

  53. Panonnummal R, Jayakumar R, Anjaneyan G, Sabitha M. In vivo anti-psoriatic activity, biodistribution, sub-acute and sub-chronic toxicity studies of orally administered methotrexate loaded chitin nanogel in comparison with methotrexate tablet. Int J Biol Macromol. Elsevier. 2018;110:259–68.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

The authors would like to thank the Indian council of medical research (ICMR), New Delhi, India, (Grant No. 45/48/2018–NAN-BMS) for providing research fellowship and the electron microscope facility of SAIF, AIIMS, New Delhi, India, is duly acknowledged.

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Correspondence to Asgar Ali.

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The protocol for in vivo animal studies comes under (“In vivo studies” section) was approved by the Institutional Animal Ethics Committee, Jamia Hamdard, New Delhi, India, (registration no. 173/GO/Re/S/2000/CPCSEA).

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Khatoon, K., Ali, A., Ahmad, F.J. et al. Novel nanoemulsion gel containing triple natural bio-actives combination of curcumin, thymoquinone, and resveratrol improves psoriasis therapy: in vitro and in vivo studies. Drug Deliv. and Transl. Res. 11, 1245–1260 (2021). https://doi.org/10.1007/s13346-020-00852-y

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