Estimation of Anti-inflammatory and Analgesic Effects of Topical NANOCEN (Nanoliposomal Arthrocen) on Mice

Abstract

The purpose of this study was to evaluate the effect of topical application of nanoliposomal avocado/soybean unsaponifiables (NANOCEN) on inflammation inhibition and pain relief in mice. NANOCEN was prepared by the injection method and characterized for vesicle size, charge, entrapment efficiency, in vitro release, and 1-month vesicle stability. The analysis of ASU formulation showed that liposomes had an average size of around 146 nm with a surface charge of − 43 mV. SEM and TEM imaging confirmed the spherical shape of the nanovesicles in ASU formulation. Moreover, ASU nanoliposomes had a high entrapment efficiency (96%) and exhibited significantly (p < 0.0001) sustained release of the drug in vitro model. The topical NANOCEN (ASU 2%) showed robust anti-inflammatory (p < 0.01) and analgesic effect (p < 0.01) superior to ibuprofen 5%. The histopathology of the inflamed tissues confirmed that the topical ASU formulation potentially (p < 0.001) inhibited infiltration of inflammatory cells. Our findings suggest that the topical formulation of NANOCEN may have local applications for pain relief in medicine.

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References

  1. 1.

    Feldman P, Khanna R. Challenging the catechism of therapeutics for chronic neuropathic pain: targeting CaV2.2 interactions with CRMP2 peptides. Neurosci Lett. 2013;557(Pt A):27–36.

    CAS  Article  Google Scholar 

  2. 2.

    Lai HC, Lin HJ, Huang ST. Chinese herbal medicine to treat urolithiasis in a patient with right flank pain and hematuria: a case report. Complement Ther Med. 2018;36:118–22.

    Article  Google Scholar 

  3. 3.

    Azizi M, Esmaeili F, Partoazar A, Ejtemaei Mehr S, Amani A. Efficacy of nano- and microemulsion-based topical gels in delivery of ibuprofen: an in vivo study. J Microencapsul. 2017;34(2):195–202.

    CAS  Article  Google Scholar 

  4. 4.

    Goudarzi R, Reid A, McDougall JJ. Evaluation of the novel avocado/soybean unsaponifiable Arthrocen to alter joint pain and inflammation in a rat model of osteoarthritis. PLoS One. 2018;13(2):e0191906.

    Article  Google Scholar 

  5. 5.

    Lippiello L, Nardo JV, Harlan R, Chiou T. Metabolic effects of avocado/soy unsaponifiables on articular chondrocytes. Evid Based Complement Alternat Med. 2008;5(2):191–7.

    Article  Google Scholar 

  6. 6.

    Joy M, Chakraborty K. Previously undisclosed bioactive sterols from corbiculid bivalve clam Villorita cyprinoides with anti-inflammatory and antioxidant potentials. Steroids. 2018;135:1–8.

    CAS  Article  Google Scholar 

  7. 7.

    de Jong A, Plat J, Mensink RP. Metabolic effects of plant sterols and stanols (review). J Nutr Biochem. 2003;14(7):362–9.

    Article  Google Scholar 

  8. 8.

    Lequesne M, Maheu E, Cadet C, Dreiser RL. Structural effect of avocado/soybean unsaponifiables on joint space loss in osteoarthritis of the hip. Arthritis Rheum. 2002;47(1):50–8.

    CAS  Article  Google Scholar 

  9. 9.

    Ernst E. Avocado-soybean unsaponifiables (ASU) for osteoarthritis - a systematic review. Clin Rheumatol. 2003;22(4–5):285–8.

    CAS  Article  Google Scholar 

  10. 10.

    Oliveira GJ, Paula LG, Souza JA, Spin-Neto R, Stavropoulos A, Marcantonio RA. Effects of avocado/soybean unsaponifiables (ASU) on the treatment of ligature-induced periodontitis in rats. Braz Oral Res. 2017;31:e28.

    PubMed  Google Scholar 

  11. 11.

    Andriamanalijaona R, Benateau H, Barre PE, Boumediene K, Labbe D, Compere JF, et al. Effect of interleukin-1beta on transforming growth factor-beta and bone morphogenetic protein-2 expression in human periodontal ligament and alveolar bone cells in culture: modulation by avocado and soybean unsaponifiables. J Periodontol. 2006;77(7):1156–66.

    CAS  Article  Google Scholar 

  12. 12.

    Boumediene K, Felisaz N, Bogdanowicz P, Galera P, Guillou GB, Pujol JP. Avocado/soya unsaponifiables enhance the expression of transforming growth factor beta1 and beta2 in cultured articular chondrocytes. Arthritis Rheum. 1999;42(1):148–56.

    CAS  Article  Google Scholar 

  13. 13.

    Gluszko P, Stasiek M. Symptom-modifying effects of oral avocado/soybean unsaponifiables in routine treatment of knee osteoarthritis in Poland. An open, prospective observational study of patients adherent to a 6-month treatment. Reumatologia. 2016;54(5):217–26.

    Article  Google Scholar 

  14. 14.

    Cevc G, Vierl U. Nanotechnology and the transdermal route: a state of the art review and critical appraisal. J Control Release. 2010;141(3):277–99.

    CAS  Article  Google Scholar 

  15. 15.

    Boileau C, Martel-Pelletier J, Caron J, Msika P, Guillou GB, Baudouin C, et al. Protective effects of total fraction of avocado/soybean unsaponifiables on the structural changes in experimental dog osteoarthritis: inhibition of nitric oxide synthase and matrix metalloproteinase-13. Arthritis Res Ther. 2009;11(2):R41.

    Article  Google Scholar 

  16. 16.

    Kianvash N, Bahador A, Pourhajibagher M, Ghafari H, Nikoui V, Rezayat SM, et al. Evaluation of propylene glycol nanoliposomes containing curcumin on burn wound model in rat: biocompatibility, wound healing, and anti-bacterial effects. Drug Deliv Transl Res. 2017;7(5):654–63.

    CAS  Article  Google Scholar 

  17. 17.

    Razavi S, Partoazar A, Takzaree N, Fasihi-Ramandi M, Bahador A, Darvishi MH. Silver sulfadiazine nanoethogel for burn healing: characterization and investigation of its in vivo effects. Nanomedicine (London). 2018;13(11):1319–31.

    CAS  Article  Google Scholar 

  18. 18.

    Bulbake U, Doppalapudi S, Kommineni N, Khan W. Liposomal formulations in clinical use: an updated review. Pharmaceutics. 2017;9(2).

  19. 19.

    Elmoslemany RM, Abdallah OY, El-Khordagui LK, Khalafallah NM. Propylene glycol liposomes as a topical delivery system for miconazole nitrate: comparison with conventional liposomes. AAPS PharmSciTech. 2012;13(2):723–31.

    CAS  Article  Google Scholar 

  20. 20.

    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.

    CAS  Article  Google Scholar 

  21. 21.

    Li WZ, Hao XL, Zhao N, Han WX, Zhai XF, Zhao Q, et al. Propylene glycol-embodying deformable liposomes as a novel drug delivery carrier for vaginal fibrauretine delivery applications. J Control Release. 2016;226:107–14.

    CAS  Article  Google Scholar 

  22. 22.

    Guindon J, De Lean A, Beaulieu P. Local interactions between anandamide, an endocannabinoid, and ibuprofen, a nonsteroidal anti-inflammatory drug, in acute and inflammatory pain. Pain. 2006;121(1–2):85–93.

    CAS  Article  Google Scholar 

  23. 23.

    Coderre TJ, Fundytus ME, McKenna JE, Dalal S, Melzack R. The formalin test: a validation of the weighted-scores method of behavioural pain rating. Pain. 1993;54(1):43–50.

    CAS  Article  Google Scholar 

  24. 24.

    Zhong X, Chen B, Yang Z. Nanocochleates as the potential delivery systems for oral antitumor of hydroxycamptothecin. J Biomed Nanotechnol. 2018;14(7):1339–46.

    CAS  Article  Google Scholar 

  25. 25.

    Elsayed MM, Abdallah OY, Naggar VF, Khalafallah NM. Lipid vesicles for skin delivery of drugs: reviewing three decades of research. Int J Pharm. 2007;332(1–2):1–16.

    CAS  Article  Google Scholar 

  26. 26.

    Au RY, Al-Talib TK, Au AY, Phan PV, Frondoza CG. Avocado soybean unsaponifiables (ASU) suppress TNF-alpha, IL-1beta, COX-2, iNOS gene expression, and prostaglandin E2 and nitric oxide production in articular chondrocytes and monocyte/macrophages. Osteoarthr Cartil. 2007;15(11):1249–55.

    CAS  Article  Google Scholar 

  27. 27.

    Partoazar A, Nasoohi S, Rezayat SM, Gilani K, Mehr SE, Amani A, et al. Nanoliposome containing cyclosporine A reduced neuroinflammation responses and improved neurological activities in cerebral ischemia/reperfusion in rat. Fundam Clin Pharmacol. 2017;31(2):185–93.

    CAS  Article  Google Scholar 

  28. 28.

    Cefalu WT, Pardridge WM. Restrictive transport of a lipid-soluble peptide (cyclosporin) through the blood-brain barrier. J Neurochem. 1985;45(6):1954–6.

    CAS  Article  Google Scholar 

  29. 29.

    Oryan A, Mohammadalipour A, Moshiri A, Tabandeh MR. Avocado/soybean unsaponifiables: a novel regulator of cutaneous wound healing, modelling and remodelling. Int Wound J. 2015;12(6):674–85.

    Article  Google Scholar 

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Acknowledgements

This research has been supported by Tehran University of Medical Sciences and Health Services grant (no. 96-04-158-37121).

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Authors

Contributions

Conceptualization: Ramin Goudarzi

Data curation: Alireza Partoazar, Sima Amini

Formal analysis: Alireza Partoazar

Funding acquisition: Tehran University of Medical Sciences

Methodology: Alireza Partoazar, Sima Amini

Project administration: Ramin Goudarzi

Resources: Ramin Goudarzi, Alireza Partoazar

Supervision: Alireza Partoazar

Validation: Ahmad Reza Dehpour

Writing—original draft: Ramin Goudarzi, Sima Amini

Corresponding author

Correspondence to Alireza Partoazar.

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Conflict of Interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the article. Dr. Ramin Goudarzi owns equity in Pharmin USA which manufactures and distributes Arthrocen.

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Goudarzi, R., Amini, S., Dehpour, A.R. et al. Estimation of Anti-inflammatory and Analgesic Effects of Topical NANOCEN (Nanoliposomal Arthrocen) on Mice. AAPS PharmSciTech 20, 233 (2019). https://doi.org/10.1208/s12249-019-1445-5

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KEY WORDS

  • Inflammation
  • Nanoliposome
  • Osteoarthritis
  • Pain
  • Treatment
  • Arthrocen
  • Avocado soy unsaponifiables