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Effect of Molecular Weight and Degree of Acetylation on Adjuvantive Properties of Chitosan Derivatives

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Abstract

The hemostatic and immunostimulating activity and cytotoxicity were determined for a number of chitosans differing in molecular weight (from 3 to 510 kDa) and degree of acetylation (from 1 to 25 mol%) that were used as adjuvants in inactivated poliomyelitic, influenza, and live influenza vaccines. It has been shown that the hemostatic activity of chitosan increased sharply with an increase in its molecular weight. In oligochitosan with a molecular weight of <16 kDa, it was smaller by a factor of 15–100 than in chitosan with a molecular weight of 20–510 kDa. The level of increase in the immunogenicity of vaccines containing oligochitosan as adjuvants was not lower than that for the vaccine including high-molecular chitosan. However, the immunostimulatory activity of oligochitosan depended on the degree of acetylation, reaching a maximum value at 6 mol%. It was shown that all oligochitosans and chitosans with a molecular mass below ~50 kDa showed almost no cytotoxicity at a concentration of ≤2.5 mg/mL, which enable their use as adjuvants for inactivated and live vaccines at the optimal ratio of molecular weight to the degree of acetylation.

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References

  1. Petrovsky, N. and Aguilar, J.C., Immunol. Cell. Biol., 2004, vol. 82, no. 5, pp. 488–496.

    Article  PubMed  CAS  Google Scholar 

  2. Petrovsky, N. and Cooper, P.D., Expert Rev. Vaccines, 2011, vol. 10, no. 4, pp. 523–537.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  3. Rinado, M., Prog. Polym. Sci., 2006, vol. 31, no. 7, pp. 603–632.

    Article  CAS  Google Scholar 

  4. Blagodatskikh, I.V., Kulikov, S.N., Vyshivannaya, O.V., Bezrodnykh, E.A., and Tikhonov, V.E., Biomacromolecules, 2017, vol. 18, no. 5, pp. 1491–1498.

    Article  PubMed  CAS  Google Scholar 

  5. Ghendon, Y., Markushin, S., Vasiliev, Y., Akopova, I., Koptiaeva, I., Krivtsov, G., Borisova, O., Ahmatova, N., and Kurbatova, E., J. Med. Virol., 2009, vol. 81, no. 3, pp. 494–506.

    Article  PubMed  CAS  Google Scholar 

  6. Arca, H.C., Gunbeyaz, M., and Senel, S., Expert Rev. Vaccines, 2009, vol. T. 8, no. 7, pp. 937–953.

    Article  PubMed  CAS  Google Scholar 

  7. Markushin, S.G., Pereverzev, A.D., Koptyaeva, I.B., Krivtsov, G.G., and Sukhno, A.S., Epidemiol. Vaktsinoprofilakt., 2010, vol. 54, no. 5, pp. 82–85.

    Google Scholar 

  8. Markushin, S.G., Gendon, Yu.Z., Krivtsov, G.G., Akopova, I.I., Sukhno, A.S., and Pereverzev, A.D., Zh. Mikrobiol. Epidemiol. Immunobiol., 2010, no. 5, pp. 29–34.

    Google Scholar 

  9. Kulikov, S.N., Lisovskaya, S.A., Zelenikhin, P.V., Bezrodnykh, E.A., Shakirova, D.R., Balgodatskikh, I.V., and Tikhonov, V.E., Eur. J. Med. Chem., 2014, vol. 74, no. 1, pp. 169–178.

    Article  PubMed  CAS  Google Scholar 

  10. Verlee, A., Mincke, S., and Stevens, C.V., Carbohydr. Polym., 2017, vol. 164, no. 1, pp. 268–283.

    Article  PubMed  CAS  Google Scholar 

  11. Kulikov, S., Tikhonov, V., Blagodatskikh, I., Bezrodnykh, E., Lopatin, S., Khairullin, R., Philippova, Y., and Abramchuk, S., Carbohyd. Polym., 2012, vol. 87, no. 1, pp. 545–550.

    Article  CAS  Google Scholar 

  12. Hirai, A., Odani, H., and Nakajima, A., Polym. Bull., 1991, vol. 26, no. 1, pp. 87–94.

    Article  CAS  Google Scholar 

  13. Kulikov, S., Zelenikhin, P., Murtazina, R., Khayrullin, R., Bezrodnikh, E., and Tikhonov, V., BioNano-Science, 2016, vol. 6, no. 4, pp. 460–463.

    Article  Google Scholar 

  14. RF Patent no. 2354695, 2016.

  15. Montomoli, E., Piccirella, S., and Khadang, B., Expert Rev. Vaccines, 2011, vol. 10, no. 7, pp. 1053–1061.

    Article  PubMed  CAS  Google Scholar 

  16. Brito, L.A. and O’Hagan, D.T., J. Control. Release, 2014, vol. 190, pp. 563–579.

    Article  PubMed  CAS  Google Scholar 

  17. Vasiliev, Y.M., Expert Rev. Vaccines, 2015, vol. 14, no. 1, pp. 37–53.

    Article  PubMed  CAS  Google Scholar 

  18. Yang, J., Tian, F., Wang, Z., Wang, O., Zeng, Y-J., and Chen, S.-Q., J. Biomed. Mater. Res. Part B: Appl. Biomater., 2008, vol. 84, no. 1, pp. 131–137.

    Article  CAS  Google Scholar 

  19. Mourya, V.K., Inamdar, N.N., and Choudhari, Y.M., Polym. Sci., 2011, vol. A53, no. 7, pp. 583–612.

    Google Scholar 

  20. Fernandes, J.C., Borges, M., Nascimento, H., Bronzeda-Rocha, E., Ramos, O.S., Pintado, M.E., and Santos-Silva, A., Int. J. Biol. Macromol., 2011, vol. 49, no. 3, pp. 433–438.

    Article  PubMed  CAS  Google Scholar 

  21. Chae, S.-Y., Jang, M.-K., and Hah, J.-W., J. Control. Release, 2005, vol. 102, no. 2, pp. 383–394.

    Article  PubMed  CAS  Google Scholar 

  22. Wu, S., Huang, Z., Yue, J., Liu, D., Wang, T., Ezano, P., Ruan, C., Zhao, X., Lu, W.W., and Pan, H., Carbohydr. Polym., 2015, vol. 132, no. 5, pp. 295–303.

    Article  PubMed  CAS  Google Scholar 

  23. Ghendon, Y., Markushin, S., Krivtsov, G., and Akopova, I.C., Arch. Virol., 2008, vol. 153, no. 5, pp. 831–837.

    Article  PubMed  CAS  Google Scholar 

  24. Blagodatskikh, I.V., Bezrodnikh, E.A., Abramchuk, S.S., Muranov, A.V., Sinitsyna, O.V., Khokhlov, A.R., and Tikhonov, V.E., J. Polym. Sci., 2013, vol. 20, no. 73, pp. 1–10.

    CAS  Google Scholar 

  25. Kurita, K., Sannan, T., and Iwakura, Y., Makromol. Chem., 1977, vol. 178, no. 12, pp. 3197–3202.

    Article  CAS  Google Scholar 

  26. Aiba, S., Int. J. Biol. Macromol., 1991, vol. 13, no. 1, pp. 40–46.

    Article  PubMed  CAS  Google Scholar 

  27. Koppolu, B.P., Smith, S.G., Ravindranathan, S., Jayanthi, S., Kumar, T.K.S., and Zaharoff, D.A., Biomaterials, 2014, vol. 35, no. 14, pp. 4382–4389.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  28. Krayukhina, M.A., Samoilova, N.A., and Yamskov, I.A., Usp. Khim., 2008, vol. 77, no. 9, pp. 854–869.

    Article  CAS  Google Scholar 

  29. Bergelson, L.D., Dyatlovitskaya, E.V., Torkhvskaya, T.I., Sorokina, I.B., and Gorkova, N.P., Biochim. Biophys. Acta, 1970, vol. 210, no. 2, pp. 287–289.

    Article  PubMed  CAS  Google Scholar 

  30. Cheung, R.C.F., Ng, T.B., Wong, J.H., and Chan, W.Y., Mar. Drugs, 2015, vol. 13, no. 8, pp. 5156–5186.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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Correspondence to V. E. Tikhonov.

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Original Russian Text © S.G. Markushin, I.I. Akopova, I.V. Blagodatskikh, S.N. Kulikov, E.A. Bezrodnykh, A.V. Muranov, I.A. Yamskov, V.E. Tikhonov, 2018, published in Prikladnaya Biokhimiya i Mikrobiologiya, 2018, Vol. 54, No. 5, pp. 513–519.

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Markushin, S.G., Akopova, I.I., Blagodatskikh, I.V. et al. Effect of Molecular Weight and Degree of Acetylation on Adjuvantive Properties of Chitosan Derivatives. Appl Biochem Microbiol 54, 512–517 (2018). https://doi.org/10.1134/S0003683818050149

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  • DOI: https://doi.org/10.1134/S0003683818050149

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