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An Agarose–Curdlan Nanogel that Carries Etanercept to Target and Neutralises TNF-α Produced by Dectin-1-Expressing Immune Cells

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Abstract

Etanercept (ETA) has been used as a drug to neutralise tumour necrotic factor alpha (TNF-α) for treatment of rheumatoid arthritis (RA), yet there are limitations concerning its low specific drug targeting and side effects. In this study, agarose–curdlan encapsulating etanercept (ACE) gel was successfully formulated and evenly distributed as nano-particles of 30–100 nm diameter, exhibiting an ETA encapsulation efficiency of 73.8% and an ETA-releasing efficiency of 50% after 52 h. The number of dectin-1-overexpressing macrophage cells, RAW264.7, exposed to ACE that migrated in the Boyden chamber assay was equal to that exposed to either agarose–curdlan or curdlan nanogels, but substantially higher than those exposed to agarose gel and water-soluble ETA by 67 and 141 fold, respectively (p < 0.05), suggesting the targeting effect of curdlan on dectin-1. Enzyme-linked immunosorbent assay revealed that the ETA released from the ACE nanogel could neutralise TNF-α secreted by lipopolysaccharide (LPS)-induced RAW264.7. Moreover, at 24 h and 72 h, the released ETA showed 1.3- to 4.4-fold greater effectiveness, respectively, than water-soluble ETA. This study demonstrates that the ACE nanogel can attract immune cells and slowly release ETA to efficiently neutralise the TNF-α produced by these cells and, thus, could be a promising ETA carrier for targeted RA treatment.

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References

  1. D.S. Dimitrov, Therapeutic Proteins (Berlin: Springer, 2012), pp. 1–26.

    Book  Google Scholar 

  2. T.S. Plantinga, J. Fransen, N. Takahashi, R. Stienstra, P.L. van Riel, W.B. van den Berg, M.G. Netea, and L.A. Joosten, Arthritis Res. Ther. 12, R26 (2010).

    Article  Google Scholar 

  3. L.M. van den Berg, E.M. Zijlstra-Willems, C.D. Richters, M.M. Ulrich, and T.B. Geijtenbeek, Cell. Immunol. 289, 49 (2014).

    Article  Google Scholar 

  4. E.H. Choy and G.S. Panayi, N. Engl. J. Med. 344, 907 (2001).

    Article  Google Scholar 

  5. C. Tetta, G. Camussi, V. Modena, C. Di Vittorio, and C. Baglioni, Ann. Rheum. Dis. 49, 665 (1990).

    Article  Google Scholar 

  6. H. Matsuno, K. Yudoh, R. Katayama, F. Nakazawa, M. Uzuki, T. Sawai, T. Yonezawa, Y. Saeki, G.S. Panayi, and C. Pitzalis, Rheumatology 41, 329 (2002).

    Article  Google Scholar 

  7. Y.-F. Chen, P. Jobanputra, P. Barton, S. Jowett, S. Bryan, W. Clark, A. Fry-Smith, and A. Burls, Health Technol. Assess. 10, 1 (2006).

    Article  Google Scholar 

  8. Z. Kaymakcalan, P. Sakorafas, S. Bose, S. Scesney, L. Xiong, D.K. Hanzatian, J. Salfeld, and E.H. Sasso, Clin. Immunol. 131, 308 (2009).

    Article  Google Scholar 

  9. K. Malottki, P. Barton, A. Tsourapas, A.O. Uthman, Z. Liu, K. Routh, M. Connock, P. Jobanputra, D. Moore, A. Fry-Smith, and Y.-F. Chen, Health Technol. Assess. 15, 1 (2011).

    Article  Google Scholar 

  10. U.G. Longo, S. Petrillo, and V. Denaro, Int. J. Rheumatol. 2015, 648073 (2015).

    Article  Google Scholar 

  11. J. Panyam and V. Labhasetwar, Adv. Drug Deliv. Rev. 55, 329 (2003).

    Article  Google Scholar 

  12. N. Wang and X.S. Wu, Int. J. Pharm. 166, 1 (1998).

    Article  Google Scholar 

  13. N. Wang and X.S. Wu, Pharm. Dev. Technol. 2, 135 (1997).

    Article  Google Scholar 

  14. P. Serwer, Agarose gels: properties and use for electrophoresis. Electrophoresis 4, 375 (1983).

    Article  Google Scholar 

  15. P. Zarrintaj, S. Manouchehri, Z. Ahmadi, M.R. Saeb, A.M. Urbanska, D.L. Kaplan, and M. Mozafari, Carbohydr. Polym. 187, 66 (2018).

    Article  Google Scholar 

  16. J. Liu, S. Lin, L. Li, and E. Liu, Int. J. Pharm. 298, 117 (2005).

    Article  Google Scholar 

  17. O. Erdemli, S. Ozen, D. Keskin, A. Usanmaz, E.D. Batu, B. Atilla, and A. Tezcaner, J. Biomater. Appl. 29, 524 (2014).

    Article  Google Scholar 

  18. M. Giulbudagian, G. Yealland, S. Hönzke, A. Edlich, B. Geisendörfer, B. Kleuser, S. Hedtrich, and M. Calderón, Theranostics 8, 450 (2018).

    Article  Google Scholar 

  19. K.B. Soo, J.I. Duck, K.J. Sik, L. Jung-heon, L.I. Young, and L.K. Bok, Biotechnol. Lett. 22, 1127 (2000).

    Article  Google Scholar 

  20. M. Kanke, K. Koda, Y. Koda, and H. Katayama, Pharm. Res. 9, 414 (1992).

    Article  Google Scholar 

  21. Z. Cai and H. Zhang, Food Hydrocoll. 68, 128 (2017).

    Article  Google Scholar 

  22. Y. Matsumura and H. Maeda, Cancer Res. 46, 6387 (1986).

    Google Scholar 

  23. X. Ma, Y. Xia, L. Ni, L. Song, and Z. Wang, Spectrochim. Acta Part A Mol. Biomol. Spectrosc. 121, 657 (2014).

    Article  Google Scholar 

  24. E.J. Lee, J.K. Park, S.A. Khan, and K.H. Lim, J. Chem. Eng. Jpn 44, 502 (2011).

    Article  Google Scholar 

  25. B.G. Zanetti-Ramos, E. Lemos-Senna, V. Soldi, R. Borsali, E. Cloutet, and H. Cramail, Polymer 47, 8080 (2006).

    Article  Google Scholar 

  26. D. Lu and A.J. Hickey, AAPS PharmSciTech 6, E641 (2005).

    Article  Google Scholar 

  27. H.C. Chen, Cell Migration (Berlin: Springer, 2005), pp. 15–22.

    Google Scholar 

  28. W. Hergert, Chapter 2. Springer Series in Optical Sciences, Vol. 169 (Berlin: Springer, 2012).

    Google Scholar 

  29. E. Al-Emam, A.G. Motawea, K. Janssens, and J. Caen, Herit. Sci. 7, 22 (2019).

    Article  Google Scholar 

  30. Y. Adachi, T. Ishii, Y. Ikeda, A. Hoshino, H. Tamura, J. Aketagawa, S. Tanaka, and N. Ohno, Infect. Immun. 72, 4159 (2004).

    Article  Google Scholar 

  31. A.S. Palma, T. Feizi, Y. Zhang, M.S. Stoll, A.M. Lawson, E. Díaz-Rodríguez, M.A. Campanero-Rhodes, J. Costa, S. Gordon, and G.D. Brown, J. Biol. Chem. 281, 5771 (2006).

    Article  Google Scholar 

  32. D.A. Salvatore, P. Carlo, C. Fabrizio, L. Ennio, M. Antonio, M. Alessandro, S. Carlo, S. Raffaele, S. Antonio, and O. Ignazio, Clin. Exp. Rheumatol. 29, 865 (2011).

    Google Scholar 

  33. X. Chen, D.C. DuBois, R.R. Almon, and W.J. Jusko, Drug Metab. Dispos. 43, 898 (2015).

    Article  Google Scholar 

  34. O.C. Farokhzad and R. Langer, ACS Nano 3, 16 (2009).

    Article  Google Scholar 

  35. M. Moscovici, C. Hlevca, C. Angela, and R.D. Pavaloiu, Nanocellulose and Nanohydrogel Matrices: Biotechnological and Biomedical Applications (Colorado: Wiley, 2017), pp. 209–269.

    Book  Google Scholar 

  36. H. Schierbeck, H. Wähämaa, U. Andersson, and H.E. Harris, Mol. Med. 16, 343 (2010).

    Article  Google Scholar 

  37. J.H. Egberts, V. Cloosters, A. Noack, B. Schniewind, L. Thon, S. Klose, B. Kettler, C. von Forstner, C. Kneitz, and J. Tepel, Can. Res. 68, 1443 (2008).

    Article  Google Scholar 

  38. S.H. Zhao, X.T. Wu, W.C. Guo, Y.M. Du, L. Yu, and J. Tang, Int. J. Pharm. 393, 269 (2010).

    Article  Google Scholar 

  39. J. Varshosaz, M.R. Zaki, M. Minaiyan, and J. Banoozadeh, Biomed. Res. Int. 2015, 571816 (2015).

    Google Scholar 

  40. Z. Hu, S. Li, and L. Yang, Polímeros 22, 422 (2012).

    Article  Google Scholar 

  41. Y. Xu, Y. Du, R. Huang, and L. Gao, Biomaterials 24, 5015 (2003).

    Article  Google Scholar 

  42. J. Han, J. Cai, W. Borjihan, T. Ganbold, T.M. Rana, and H. Baigude, Carbohydr. Polym. 117, 324 (2015).

    Article  Google Scholar 

  43. S. Mochizuki and K. Sakurai, J. Control. Release 151, 155 (2011).

    Article  Google Scholar 

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Acknowledgement

This work was supported by a grant from Vietnam National University, Hanoi to Huong T. T.Pham Under project number KLEPT.16.01. We thank Msc. Phan Thi Kieu Trang from the Faculty of Environmental Engineering, University of Kitakyushu for her kind guidance on setting the drug targeting experiment, and Dr. Pham Bao Yen from the Key Laboratory of Enzyme and Protein Technology, VNU University of Science, Vietnam National University-Hanoi for English correction

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Author notes

  1. Dung H. T. Nguyen and Ngoc B. Nguyen have contributed to this work equally.

Authors and Affiliations

  1. Key Laboratory of Enzyme and Protein Technology, VNU University of Science, Vietnam National University, 334 Nguyen Trai, Thanh Xuan, Hanoi, Vietnam

    Dung H. T. Nguyen, Ngoc B. Nguyen, Linh T. P. Nguyen, Ly T. Do, Tung T. Nguyen, Thang D. Nguyen, Anh T. V. Nguyen & Huong T. T. Pham

  2. Nano and Energy Research Center, Faculty of Physics, VNU University of Science, Vietnam National University, 334 Nguyen Trai, Thanh Xuan, Hanoi, Vietnam

    Nam H. Nguyen

  3. Department of Chemistry and Biochemistry, University of Kitakyushu, 1-1, Hibikino, Wakamatsu-ku, Kitakyushu, Fukuoka, 808-0135, Japan

    Sakurai Kazuo & Mochizuki Shinichi

  4. Department of Life and Environment Engineering, Faculty of Environmental Engineering, University of Kitakyushu, Kitakyushu, Fukuoka, 808-0135, Japan

    Kihara Takanori

Authors
  1. Dung H. T. Nguyen
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  2. Ngoc B. Nguyen
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  3. Linh T. P. Nguyen
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  5. Tung T. Nguyen
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  9. Kihara Takanori
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  11. Anh T. V. Nguyen
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  12. Huong T. T. Pham
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Correspondence to Huong T. T. Pham.

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Nguyen, D.H., Nguyen, N.B., Nguyen, L.T. et al. An Agarose–Curdlan Nanogel that Carries Etanercept to Target and Neutralises TNF-α Produced by Dectin-1-Expressing Immune Cells. J. Electron. Mater. 48, 6570–6582 (2019). https://doi.org/10.1007/s11664-019-07458-2

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  • DOI: https://doi.org/10.1007/s11664-019-07458-2

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