A Comparative Study of Levocetirizine Loaded Vesicular and Matrix Type System for Topical Application: Appraisal of Therapeutic Potential against Atopic Dermatitis

Abstract

Background

Topical drug delivery offers improved therapeutic effect and reduced systemic adverse effects of the administered compounds.

Objective

The present work was aimed at developing and comparing levocetirizine loaded polymeric nanoparticles and niosomal formulation(s), respectively, against dinitrochlorobenzene-induced atopic dermatitis animal model.

Methods

The niosome and chitosan nanoparticle were developed and evaluated for particle size distribution, drug loading, and entrapment efficiency. The formulations were optimized through Box-Behnken design. The optimized formulations were dispersed in carbopol gel and evaluated for ex vivo permeation, retention, and in vivo studies.

Results

The optimized niosomes and chitosan nanoparticle exhibited a particle size range of 384.4 ± 64.3 nm and 382.7 ± 59.2 nm, drug loading of 18.99 ± 0.02% and 12.2 ± 1.6%, and entrapment efficiency of 46.63 ± 2.12% and 29.6 ± 1.6%, respectively. The permeation and retention studies displayed less permeation and significantly (p < 0.01) high retention percentage of LCZD by OPT-N gel when compared with OPT-CN gel. In in vivo studies revealed that OPT-N significantly (p < 0.05) reduces erythema score (from 3 to 1) and scratching frequency (70–25 scratches/20 min).

Conclusion

OPT-N gel shows high entrapment efficiency and skin retention capacity of the drug along with better topical applicability and higher therapeutic efficacy. The OPT-N also manifested the maximum peripheral action of LCZD against AD as compared with optimized chitosan gel and plain LCZD gel.

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References

  1. 1.

    Pal RR, Parashar P, Singh I, Saraf SA. Tamanu oil potentiated novel sericin emulgel of levocetirizine: repurposing for topical delivery against DNCB-induced atopic dermatitis, QbD based development and in vivo evaluation. 2019;36:1–15. https://doi.org/10.1080/02652048.2019.1637474.

  2. 2.

    Akhtar N, Verma A, Pathak K. Exploring preclinical and clinical effectiveness of nanoformulations in the treatment of atopic dermatitis: safety aspects and patent reviews. Bull Fac Pharm Cairo Univ. 2017;55(1):1–10. https://doi.org/10.1016/j.bfopcu.2016.12.003.

    Article  Google Scholar 

  3. 3.

    Guttman-Yassky E, Dhingra N, Leung DY. New era of biologic therapeutics in atopic dermatitis. Expert Opin Biol Ther. 2013;13(4):549–61. https://doi.org/10.1517/14712598.2013.758708.

    CAS  Article  PubMed  Google Scholar 

  4. 4.

    Shao M, Hussain Z, Thu HE, Khan S, Katas H, Ahmed TA, et al. Drug nanocarrier, the future of atopic diseases: advanced drug delivery systems and smart management of disease. Colloids Surf B: Biointerfaces. 2016;147:475–91. https://doi.org/10.1016/j.colsurfb.2016.08.027.

    CAS  Article  PubMed  Google Scholar 

  5. 5.

    Nutten S. Atopic dermatitis: global epidemiology and risk factors. Ann Nutr Metab. 2015;66(Suppl 1):8–16. https://doi.org/10.1159/000370220.

    CAS  Article  PubMed  Google Scholar 

  6. 6.

    Snidvongs K, Seresirikachorn K, Khattiyawittayakun L, Chitsuthipakorn W. Sedative effects of Levocetirizine: a systematic review and meta-analysis of randomized controlled studies. Drugs. 2017;77(2):175–86. https://doi.org/10.1007/s40265-016-0682-0.

    CAS  Article  PubMed  Google Scholar 

  7. 7.

    Goindi S, Kumar G, Kaur A. Novel flexible vesicles based topical formulation of levocetirizine: in vivo evaluation using oxazolone-induced atopic dermatitis in murine model. J Liposome Res. 2014;24(3):249–57. https://doi.org/10.3109/08982104.2014.899365.

    CAS  Article  PubMed  Google Scholar 

  8. 8.

    Singh N, Parashar P, Tripathi CB, Kanoujia J, Kaithwas G, Saraf SA. Oral delivery of allopurinol niosomes in treatment of gout in animal model. J Liposome Res. 2017;27(2):130–8. https://doi.org/10.1080/08982104.2016.1174943.

    CAS  Article  PubMed  Google Scholar 

  9. 9.

    Abidin L, Mujeeb M, Imam SS, Aqil M, Khurana D. Enhanced transdermal delivery of luteolin via non-ionic surfactant-based vesicle: quality evaluation and anti-arthritic assessment. Drug Deliv. 2016;23(3):1069–74.

    CAS  Article  Google Scholar 

  10. 10.

    Dong W, Wang X, Liu C, Zhang X, Zhang X, Chen X, et al. Chitosan based polymer-lipid hybrid nanoparticles for oral delivery of enoxaparin. Int J Pharm. 2018;547(1):499–505. https://doi.org/10.1016/j.ijpharm.2018.05.076.

    CAS  Article  PubMed  Google Scholar 

  11. 11.

    Kalam MA. Development of chitosan nanoparticles coated with hyaluronic acid for topical ocular delivery of dexamethasone. Int J Biol Macromol. 2016;89:127–36. https://doi.org/10.1016/j.ijbiomac.2016.04.070.

    CAS  Article  PubMed  Google Scholar 

  12. 12.

    Fakhria A, Gilani SJ, Imam SS. Formulation of thymoquinone loaded chitosan nano vesicles: in-vitro evaluation and in-vivo anti-hyperlipidemic assessment. J Drug Deliv Sci Technol. 2019;50:339–46.

    CAS  Article  Google Scholar 

  13. 13.

    Casanova F, Estevinho BN, Santos L. Preliminary studies of rosmarinic acid microencapsulation with chitosan and modified chitosan for topical delivery. Powder Technol. 2016;297:44–9. https://doi.org/10.1016/j.powtec.2016.04.014.

    CAS  Article  Google Scholar 

  14. 14.

    Noor NM, Sheikh K, Somavarapu S, Taylor KMG. Preparation and characterization of dutasteride-loaded nanostructured lipid carriers coated with stearic acid-chitosan oligomer for topical delivery. Eur J Pharm Biopharm. 2017;117:372–84. https://doi.org/10.1016/j.ejpb.2017.04.012.

    CAS  Article  PubMed  Google Scholar 

  15. 15.

    Michailidou G, Christodoulou E, Nanaki S, Barmpalexis P, Karavas E, Vergkizi-Nikolakaki S, et al. Super-hydrophilic and high strength polymeric foam dressings of modified chitosan blends for topical wound delivery of chloramphenicol. Carbohydr Polym. 2019;208:1–13. https://doi.org/10.1016/j.carbpol.2018.12.050.

    CAS  Article  PubMed  Google Scholar 

  16. 16.

    Solé I, Vílchez S, Miras J, Montanyà N, García-Celma MJ, Esquena J. DHA and l-carnitine loaded chitosan hydrogels as delivery systems for topical applications. Colloids Surf A Physicochem Eng Asp. 2017;525:85–92. https://doi.org/10.1016/j.colsurfa.2017.04.056.

    CAS  Article  Google Scholar 

  17. 17.

    Gibson M. Pharmaceutical preformulation and formulation: a practical guide from candidate drug selection to commercial dosage form. CRC Press; 2016.

  18. 18.

    Pengnam S, Patrojanasophon P, Rojanarata T, Ngawhirunpat T. Yingyongnarongkul B-e, Radchatawedchakoon W et al. a novel plier-like gemini cationic niosome for nucleic acid delivery. J Drug Deliv Sci Technol. 2019;52:325–33. https://doi.org/10.1016/j.jddst.2019.04.032.

    CAS  Article  Google Scholar 

  19. 19.

    Avadi MR, Sadeghi AM, Mohammadpour N, Abedin S, Atyabi F, Dinarvand R, et al. Preparation and characterization of insulin nanoparticles using chitosan and Arabic gum with ionic gelation method. Nanomed Nanotechnol Biol Med. 2010;6(1):58–63. https://doi.org/10.1016/j.nano.2009.04.007.

    CAS  Article  Google Scholar 

  20. 20.

    Kanoujia J, Singh M, Singh P, Saraf SA. Novel genipin crosslinked atorvastatin loaded sericin nanoparticles for their enhanced antihyperlipidemic activity. Mater Sci Eng C. 2016;69:967–76.

    CAS  Article  Google Scholar 

  21. 21.

    Mukherjee B, Patra B, Layek B, Mukherjee A. Sustained release of acyclovir from nano-liposomes and nano-niosomes: an in vitro study. Int J Nanomedicine. 2007;2(2):213.

    CAS  PubMed  PubMed Central  Google Scholar 

  22. 22.

    Singh M, Kanoujia J, Singh P, Tripathi CB, Arya M, Parashar P, et al. Development of an α-linolenic acid containing soft nanocarrier for oral delivery: in vitro and in vivo evaluation. RSC Adv. 2016;6(81):77590–602.

    CAS  Article  Google Scholar 

  23. 23.

    Verma J, Kanoujia J, Parashar P, Tripathi CB, Saraf SA. Wound healing applications of sericin/chitosan-capped silver nanoparticles incorporated hydrogel. Drug Deliv Transl Res. 2017;7(1):77–88. https://doi.org/10.1007/s13346-016-0322-y.

    CAS  Article  PubMed  Google Scholar 

  24. 24.

    Hay RJ, Johns NE, Williams HC, Bolliger IW, Dellavalle RP, Margolis DJ, et al. The global burden of skin disease in 2010: an analysis of the prevalence and impact of skin conditions. J Invest Dermatol. 2014;134(6):1527–34. https://doi.org/10.1038/jid.2013.446.

    CAS  Article  PubMed  Google Scholar 

  25. 25.

    Siddique MI, Katas H, Jamil A, Amin MCIM, Ng S-F, Zulfakar MH, et al. Potential treatment of atopic dermatitis: tolerability and safety of cream containing nanoparticles loaded with hydrocortisone and hydroxytyrosol in human subjects. Drug Deliv Transl Res. 2019;9(2):469–81.

    CAS  Article  Google Scholar 

  26. 26.

    Yamamoto M, Haruna T, Yasui K, Takahashi H, Iduhara M, Takaki S, et al. A novel atopic dermatitis model induced by topical application with dermatophagoides farinae extract in NC/Nga mice. Allergol Int. 2007;56(2):139–48.

    Article  Google Scholar 

  27. 27.

    Barbosa AI, Costa Lima SA, Reis S. Development of methotrexate loaded fucoidan/chitosan nanoparticles with anti-inflammatory potential and enhanced skin permeation. Int J Biol Macromol. 2019;124:1115–22. https://doi.org/10.1016/j.ijbiomac.2018.12.014.

    CAS  Article  PubMed  Google Scholar 

  28. 28.

    Moghddam SRM, Ahad A, Aqil M, Imam SS, Sultana Y. Formulation and optimization of niosomes for topical diacerein delivery using 3-factor, 3-level box-Behnken design for the management of psoriasis. Mater Sci Eng C. 2016;69:789–97. https://doi.org/10.1016/j.msec.2016.07.043.

    CAS  Article  Google Scholar 

  29. 29.

    Imam SS, Aqil M, Akhtar M, Sultana Y, Ali A. Formulation by design-based proniosome for accentuated transdermal delivery of risperidone: in vitro characterization and in vivo pharmacokinetic study. Drug Deliv. 2015;22(8):1059–70.

    CAS  Article  Google Scholar 

  30. 30.

    Rawat D, Tripathi CB, Parashar P, Singh M, Kaithwas G, Saraf SA. Development and characterization of nanostructured lipid carriers of Vetiveria zizanoides oil for therapeutic potential in prickly heat treatment. J Pharm Sci Pharmacol. 2015;2(2):162–71.

    Article  Google Scholar 

  31. 31.

    Liu X, Shen B, Shen C, Zhong R, Wang X, Yuan H. Nanoparticle-loaded gels for topical delivery of nitrofurazone: effect of particle size on skin permeation and retention. J Drug Deliv Sci Technol. 2018;45:367–72. https://doi.org/10.1016/j.jddst.2018.04.005.

    CAS  Article  Google Scholar 

  32. 32.

    Rehman K, Zulfakar MH. Recent advances in gel technologies for topical and transdermal drug delivery. Drug Dev Ind Pharm. 2014;40(4):433–40.

    CAS  Article  Google Scholar 

  33. 33.

    Chen H, Chang X, Du D, Li J, Xu H, Yang X. Microemulsion-based hydrogel formulation of ibuprofen for topical delivery. Int J Pharm. 2006;315(1–2):52–8.

    CAS  Article  Google Scholar 

  34. 34.

    Savin C-L, Popa M, Delaite C, Costuleanu M, Costin D, Peptu CA. Chitosan grafted-poly(ethylene glycol) methacrylate nanoparticles as carrier for controlled release of bevacizumab. Mater Sci Eng C. 2019;98:843–60. https://doi.org/10.1016/j.msec.2019.01.036.

    CAS  Article  Google Scholar 

  35. 35.

    Meng S, Sun L, Wang L, Lin Z, Liu Z, Xi L, et al. Loading of water-insoluble celastrol into niosome hydrogels for improved topical permeation and anti-psoriasis activity. Colloids Surf B: Biointerfaces. 2019;182:110352. https://doi.org/10.1016/j.colsurfb.2019.110352.

    CAS  Article  PubMed  Google Scholar 

  36. 36.

    Aggarwal N, Goindi S. Preparation and evaluation of antifungal efficacy of griseofulvin loaded deformable membrane vesicles in optimized Guinea pig model of Microsporum canis--dermatophytosis. Int J Pharm. 2012;437(1–2):277–87. https://doi.org/10.1016/j.ijpharm.2012.08.015.

    CAS  Article  PubMed  Google Scholar 

  37. 37.

    Wichayapreechar P, Anuchapreeda S. Dermal targeting of Centella asiatica extract using hyaluronic acid surface modified niosomes. 2019;30:1–11. https://doi.org/10.1080/08982104.2019.1614952.

  38. 38.

    Chen S, Hanning S, Falconer J, Locke M, Wen J. Recent advances in non-ionic surfactant vesicles (niosomes): fabrication, characterization, pharmaceutical and cosmetic applications. Eur J Pharm Biopharm. 2019;144:18–39. https://doi.org/10.1016/j.ejpb.2019.08.015.

    CAS  Article  PubMed  Google Scholar 

  39. 39.

    Pradhan S, Moore KM, Ainslie KM. Flexible, microstructured surfaces using chitin-derived biopolymers. 2019;7(35):5328–35. https://doi.org/10.1039/c9tb00965e.

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Correspondence to Shubhini A. Saraf.

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Pal, R.R., Maurya, A.K., Parashar, P. et al. A Comparative Study of Levocetirizine Loaded Vesicular and Matrix Type System for Topical Application: Appraisal of Therapeutic Potential against Atopic Dermatitis. J Pharm Innov (2020). https://doi.org/10.1007/s12247-020-09465-x

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Keywords

  • Carbopol
  • Niosomes
  • Arabic gum
  • Chitosan
  • Pharmacodynamic