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Skin targeting of resveratrol utilizing solid lipid nanoparticle-engrossed gel for chemically induced irritant contact dermatitis

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Abstract

Irritant contact dermatitis (ICD) is a chronic and relapsing skin disease with severe eczematous lesions. Despite its growing prevalence, therapeutic treatments remain limited. Long-term topical corticosteroid treatment can induce skin atrophy, hypopigmentation, and increase in transepidermal water loss. An innovative dermal treatment is essential to reduce the side effects of corticosteroids. Topical resveratrol (RES), although effective for ICD, is a challenging molecule due to low solubility and poor bioavailability. The objective of this work was to build RES-loaded solid lipid nanoparticles (RES-SLNs) with skin targeting. For this purpose, RES-SLNs were prepared using the probe ultrasonication method utilizing Precirol ATO 5 and Tween 20. The RES-SLNs were evaluated for particle size, entrapment efficiency (EE), and transmission electron microscopy (TEM) studies. Further, RES-SLNs were incorporated into Carbopol gel and investigated for ex vivo skin permeation, deposition study on human cadaver skin, and finally skin irritation study on New Zealand White rabbits. It was further assessed for possible beneficial effects on ICD using BALB/c mice. RES-SLN showed mean size below 100 nm and 68–89% EE. TEM studies confirmed spherical particles in the nanometer range. An ex vivo study of RES-SLN-loaded gel exhibited controlled drug release up to 24 h; similarly, in vitro drug deposition studies showed potential of skin targeting with no skin irritation. RES-SLN gel confirmed competent suppression of ear swelling and reduction in skin water content in the BALB/c mouse model of ICD when compared to marketed gel. Thus, the formulated RES-SLN gel would be a safe and effective alternative to conventional vehicles for treatment of ICD.

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References

  1. Slodownik D, Lee A, Nixon R. Irritant contact dermatitis: a review. Australas J Dermatol. 2008;49:1–11.

    Article  PubMed  Google Scholar 

  2. Han MH, Yoon WK, Lee H, Han SB, Lee K, Park SK, Yang KH, Kim HM, Kang JS. Topical application of silymarin reduces chemical-induced irritant contact dermatitis in BALB/c mice. Int Immunopharmacol. 2007;7:1651–8.

    Article  CAS  PubMed  Google Scholar 

  3. Bose S, Kohn BM. Preparation of lipid based nanosystems for topical delivery of quercetin. Eur J Pharm Sci. 2013;48:442–52.

    Article  CAS  PubMed  Google Scholar 

  4. Sivaranjani N, Rao VS, Rajeev G. Role of reactive oxygen species and antioxidants in atopic dermatitis. J Clin Diagn Res. 2013;7(12):2683–5.

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Russell JJ. Topical tacrolimus: a new therapy for atopic dermatitis. Am Family Phys. 2002;66(10):1899–903.

    Google Scholar 

  6. Jung SH, Cho YS, Jun SS, Koo JS, Cheon HG, Shin BC. Topical application of liposomal cobalamin hydrogel for atopic dermatitis therapy. Pharmazie. 2011;66:430–5.

    CAS  PubMed  Google Scholar 

  7. Yun Y, Kim K, Choi I, Ko SG. Topical herbal application in the management of atopic dermatitis: a review of animal studies. Mediat Inflamm. 2014; doi:10.1155/2014/752103.

    Google Scholar 

  8. Ndiayea M, Philippea C, Mukhtara H, Ahmada N. The grape antioxidant resveratrol for skin disorders: promise, prospects and challenges. Arch Biochem Biophys. 2011;508(2):164–70.

    Article  Google Scholar 

  9. Sale S, Verschoyle RD, Boocock D, Jones DJL, Wilsher N, Ruparelia KC, Potter GA, Farmer PB, Steward WP, Gescher A. Pharmacokinetics in mice and growth-inhibitory properties of the putative cancer chemopreventive agent resveratrol and the synthetic analogue trans 3,4,5,4′-tetramethoxystilbene. Br J Cancer. 2004;90:736–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Pai VV, Shukla P, Kikkeri NN. Antioxidant in dermatology. Indian Dermatol. 2014;5(2):210–4.

    Article  Google Scholar 

  11. Souto EB, Almeida AJ, Muller RH. Lipid nanoparticles (SLN®, NLC®) for cutaneous drug delivery: structure, protection and skin effects. J Biomed Nanotechnol. 2007;3:317–31.

    Article  CAS  Google Scholar 

  12. Schafer KM, Mehnert W, Korting HC. Lipid nanoparticles for improved topical application of drugs for skin diseases. Adv Drug Deliv Rev. 2007;59:427–43.

    Article  Google Scholar 

  13. Pardeike J, Hommoss A, Müller RH. Lipid nanoparticles (SLN, NLC) in cosmetic and pharmaceutical dermal products. Int J Pharm. 2009;366(1–2):170–84.

    Article  CAS  PubMed  Google Scholar 

  14. He H, Chen X, Wang G, et al. High-performance liquid chromatography spectrometric analysis of trans-resveratrol in rat plasma. J Chromatogr B. 2006;832(2):177–80.

    Article  CAS  Google Scholar 

  15. Ranpise NS, Korabu SS, Ghodake VN. Second generation lipid nanoparticles (NLC) as an oral drug carrier for delivery of lercanidipine hydrochloride. Colloids Surf B: Biointerfaces. 2014;116:81–7.

  16. Fang JU, Fang CL, Liu CH, Su YH. Lipid nanoparticles as vehicles for topical psoralen delivery: solid lipid nanoparticles (SLN) versus nanostructured lipid carriers (NLC). Eur J Pharm Biopharm. 2008;70:633–40.

    Article  CAS  PubMed  Google Scholar 

  17. Mehnert W, Mader K. Solid lipid nanoparticles: production, characterization and applications. Adv Drug Deliv Rev. 2001;47:165–96.

    Article  CAS  PubMed  Google Scholar 

  18. Padamwar MN, Pokharkar VB. Development of vitamin loaded topical liposomal formulation using factorial design approach: drug deposition and stability. Int J Pharm. 2006;320:37–44.

    Article  CAS  PubMed  Google Scholar 

  19. Souto EB, Doktorovová S, Araújo J, Garcia ML, Rakovsk E. Formulating fluticasone propionate in novel PEG-containing nanostructured lipid carriers (PEG-NLC). Colloids Surf B : Biointerfaces. 2010;75:538–42.

    Article  PubMed  Google Scholar 

  20. Wang D, Zhao P, Zhang C, Zhang R, Li X, Cui F. Preparation and characterization of total flavones of Hippophae rhamnoides (TFH) solid lipid nanoparticles by heating-ultrasonic dispersion and lyophilization. J Pharm Sci. 2006;1:205–12.

    CAS  Google Scholar 

  21. Sonawane R, Harde H, Katariya M, Agrawal S, Jain S. Solid lipid nanoparticles-loaded topical gel containing combination drugs : an approach to offset psoriasis. Expert Opin Drug Deliv. 2014;11(12):1–15.

    Article  Google Scholar 

  22. Bikkad ML, Nathani AH, Mandlik SK, Shrotriya SN, Ranpise NS. Halobetasol propionate-loaded solid lipid nanoparticles (SLN) for skin targeting by topical delivery. J Liposome Res. 2013;2104:1–11.

    Google Scholar 

  23. Wissing SA, Lippacher A, Muller RH. Investigation on occlusive properties of solid lipid nanoparticles (SLN). J Cosmet Sci. 2001;52:313–24.

    CAS  PubMed  Google Scholar 

  24. Kevin PA, Saleh MA. Free radical scavenging and antioxidant activities of silymarin components. Antioxidants. 2013;2:398–407.

    Article  Google Scholar 

  25. Pople PV, Singh KK. Development and evaluation of topical formulation containing solid lipid nanoparticles of vitamin A. AAPS Pharm Sci Tech. 2006;7(4):91. E1-E7

    Article  Google Scholar 

  26. Vaghasiya H, Kumar A, Sawant K. Development of solid lipid nanoparticles based controlled release system for topical delivery of terbinafine hydrochloride. Eur J Pharm Sci. 2013;49(2):311–22.

    Article  CAS  PubMed  Google Scholar 

  27. Mandawgade SD, Patravale VB. Development of SLNs from natural lipids: application to topical delivery of tretinoin. Int J Pharm. 2008;363(1–2):132–8.

    Article  CAS  PubMed  Google Scholar 

  28. Pople PV, Singh KK. Development and evaluation of colloidal modified nanolipid carrier: application to topical delivery of tacrolimus, part II—in vivo assessment, drug targeting, efficacy and safety in treatment of atopic dermatitis. Eur J Pharm Biopharm. 2012;84(2013):72–83.

    PubMed  Google Scholar 

  29. Bhalekar MR, Upadhaya PP, Madgulkar AR. Formulation and evaluation of Adapalene-loaded nanoparticulates for epidermal localization. Drug Deliv Transl Res. 2015;5(6):585–95.

    Article  CAS  PubMed  Google Scholar 

  30. Wavikar P, Vavia PR. Nanolipidgel for enhanced skin deposition and improved antifungal activity. AAPS PharmSciTech. 2013;14(1):222–33.

    Article  CAS  PubMed  Google Scholar 

  31. Dinarvand R, Moghadam SH, Sheikhi A, Atyabi F. Effect of surfactant HLB and different formulation variables on the properties of poly-D,L-lactide microspheres of naltrexone prepared by double emulsion technique. J Microencapsul. 2005;22(2):139–51.

    Article  CAS  PubMed  Google Scholar 

  32. Kharia AA, Singhai AK, Verma R. Formulation and evaluation of polymeric nanoparticles of an antiviral drug for gastroretention. Int J Pharm Sci Nanotech. 2012;4(4):1557–62.

    Google Scholar 

  33. Levy MY, Schutze W, Fuhrer C, Benita S. Characterization of diazepam submicron emulsion interface: role of oleic acid. J Microencapsul. 1994;11:79–92.

    Article  CAS  PubMed  Google Scholar 

  34. Liu J, Hu W, Chen H, et al. Isotretinoin-loaded solid lipid nanoparticles with skin targeting for topical delivery. Int J Pharm. 2007;328:191–5.

    Article  CAS  PubMed  Google Scholar 

  35. Patil SS, Venugopal E, Bhat S, Mahadik KR, Paradkar AR. Probing influence of mesophasic transformation on performance of self-emulsifying system: effect of ion. Mol Pharm. 2012;9:318–24.

    Article  CAS  PubMed  Google Scholar 

  36. Shah M, Pathak K. Development and statistical optimization of solid lipid nanoparticles of simvastatin by using 23 full-factorial design. AAPS Pharm Sci Tech. 2010;11(2):489–96.

    Article  CAS  Google Scholar 

  37. Schubert MA, Muller-Goymann CC. Solvent injection as a new approach for manufacturing lipid nanoparticles—evaluation of the method and process parameters. Eur J Pharm Biopharm. 2003;55:125–31.

    Article  CAS  PubMed  Google Scholar 

  38. Bunjes H, Unruh T. Characterization of lipid nanoparticles by differential scanning calorimetry, X-ray and neutron scattering. Adv Drug Deliv Rev. 2007;59:379–402.

    Article  CAS  PubMed  Google Scholar 

  39. Hou D, Xie C, Huang K, Zhu C. The production and characteristics of solid lipid nanoparticles (SLNs). Biomaterials. 2003;24:1781–5.

    Article  CAS  PubMed  Google Scholar 

  40. Pardeike J, Hommoss A, Müller RH. Lipid nanoparticles (SLN, NLC) in cosmetic and pharmaceutical dermal products. Int J Pharm. 2009;366(1(2)):170–84.

    Article  CAS  PubMed  Google Scholar 

  41. Freitas C, Muller RH. Stability determination of solid lipid nanoparticles (SLN) in aqueous dispersion after addition of electrolyte. J Microencapsul. 1999;16:59–71.

    Article  CAS  PubMed  Google Scholar 

  42. Freitas C, Müller RH. Correlation between long-term stability of solid lipid nanoparticles (SLN™) and crystallinity of the lipid phase. Eur J Pharm Biopharm. 1999;47:125–32.

    Article  CAS  PubMed  Google Scholar 

  43. Wang YY, Hong CT, Chiu WT, Fang JY. In vitro and in vivo evaluations of topically applied capsaicin and nonivamide from hydrogels. Int J Pharm. 2001;224:89–104.

    Article  CAS  PubMed  Google Scholar 

  44. Sanna V, Gavini E, Cossu M, et al. Solid lipid nanoparticles (SLN) as carriers for the topical delivery of econazole nitrate: in-vitro characterization, ex-vivo and in-vivo studies. J Pharm Pharmacol. 2007;59:1057–64.

    Article  CAS  PubMed  Google Scholar 

  45. Jenning V, Gysler A, Schafer-Korting M, Gohla SH. Vitamin A loaded solid lipid nanoparticles for topical use: occlusive properties and drug targeting to the upper skin. Eur J Pharm Biopharm. 2003;49:211–8.

    Article  Google Scholar 

  46. Wissing SA, Muller RH. The influence of the crystallinity of lipid nanoparticles on their occlusive properties. Int J Pharm. 2002;242:377–89.

    Article  CAS  PubMed  Google Scholar 

  47. Cevc G. Lipid vesicles and other colloids as drug carriers on the skin. Adv Drug Deliv Rev. 2004;56:675–711.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We appreciate the generosity and cooperation of Gattefosse, India, Lubrizol, India, for the samples of excipients employed during the current studies.

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Authors and Affiliations

  1. Sinhgad College of Pharmacy, Vadgaon(Bk.), Pune S. No 44/1, Vadgaon (Bk), Off Sinhgad Road, Pune, MS, 411041, India

    S. N. Shrotriya, N. S. Ranpise & B. V. Vidhate

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  1. S. N. Shrotriya
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  2. N. S. Ranpise
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  3. B. V. Vidhate
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Correspondence to S. N. Shrotriya.

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All the experimental procedures used in this study were reviewed and followed by an Institutional Animal Ethics Committee of STES’s Sinhgad College of Pharmacy, Pune, constituted under the Committee for Purpose of Control and Supervision of Experiments on Animals (CPCSEA).

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The authors declare that they have no conflict of interest.

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Shrotriya, S.N., Ranpise, N.S. & Vidhate, B.V. Skin targeting of resveratrol utilizing solid lipid nanoparticle-engrossed gel for chemically induced irritant contact dermatitis. Drug Deliv. and Transl. Res. 7, 37–52 (2017). https://doi.org/10.1007/s13346-016-0350-7

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