Functional derivatives of chitosan, soluble in neutral medium as drugs and genetic material carrier: preparation and properties

Cover Page

Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription Access

Abstract

Method of chitosan modification, providing controlled addition of the quaternized block has been proposed. The structure of the products obtained were studied by FT-IR and NMR spectroscopy; their solubility and acid-base properties was characterized by turbodimetry and potentiometry, respectively. Presence about 50% of quaternized amino groups was shown to be necessary to obtain soluble products. The difference in pH-sensitivity of modified derivatives with different types of quaternized block attachment was revealed by studying their interaction with a model polystyrene sulfonate anion. The possibility of preparing complexes based on the obtained derivatives with DNA — polyplexes, stable under conditions close to physiological ones has been demonstrated. It was shown the presence of primary amino groups on the polycation chains leads to a decrease in the polyplexe size. The data obtained can form the basis for development of drug and genetic material delivery system.

The 2-stage method of chitosan modification providing controlled addition of the quaternized block has been proposed. The structure of the products obtained were studied by FT-IR and NMR spectroscopy; their solubility and acid-base properties was characterized by turbodimetry and potentiometry, respectively. The presence about 50% of quaternized amino groups was shown to be necessary to obtain soluble products. The difference in pH-sensitivity of modified derivatives with different types of quaternized block attachment was revealed by studying their interaction with a model polystyrene sulfonate anion. The possibility of preparing complexes based on the obtained derivatives with DNA, polyplexes stable under conditions close to physiological ones has been demonstrated. It is shown that the presence of primary amino groups on the polycation chains leads to a decrease in the polyplexe size. The data obtained can form the basis for development of drug and genetic material delivery systems.

Full Text

Restricted Access

About the authors

M. Yu. Gorshkova

A. V. Topchiev Institute of Petrochemical Synthesis RAS

Author for correspondence.
Email: mgor@ps.ac.ru
Russian Federation, 119991, Moscow

E. S. Gigoryan

A. V. Topchiev Institute of Petrochemical Synthesis RAS

Email: mgor@ps.ac.ru
Russian Federation, 119991, Moscow

I. F. Volkova

A. V. Topchiev Institute of Petrochemical Synthesis RAS

Email: mgor@ps.ac.ru
Russian Federation, 119991, Moscow

References

  1. Harugade A., Sherje A. P., Pethe А. // React. Func. Polym. 2023. V. 191. P. 105634. https://doi.org/10.1016/j.reactfunctpolym.2023.105634
  2. Verma D., Okhawilai M., Goh K. L., Thakur K. V., Senthilkumar N., Sharma M., Uyama H. // Environ. Res. 2023. V. 235. P. 116580. https://doi.org/10.1016/j.envres.2023.116580
  3. Горшенин Д. С., Жернов Ю. В., Кривцов Г. Г., Хаитов М. Р. // Иммунология. 2020. Т. 41. № 5. C. 470–478. https://doi.org/10.33029/0206-4952-2020-41-5-470-478
  4. Iqbal Y., Ahmed I., Irfan M. F., Chatha S. A. S., Zubair M., Ullah A. // Carbohyd. Polym. 2023. Р. 121318. https://doi.org/10.1016/j.carbpol.2023.121318
  5. Tang W., Wang J., Hou H., Li Y., Wang J., Fu J. et al. // Int. J. Biol. Macromol. 2023. V. 240. P. 124398. https://doi.org/10.1016/j.ijbiomac.2023.124398
  6. Горшкова М. Ю., Волкова И. Ф., Алексеева С. Г., Молоткова Н. Н., Скорикова Е. Е., Изумрудов В. А. // Высокомо-лекулярные cоединения. Сер. А. 2011. Т. 53. № 1. C. 60–69.
  7. Yevlampieva N. P., Gubarev A. S., Gorshkova M. Yu., Okrugin B. M., Ryumtsev E. I. // J. Polym. Res. 2015. V. 22. P. 166. https://doi.org/10.1007/s10965-015-0802-7
  8. Izumrudov V. A., Volkova I. F., Gorshkova M. Yu. // Eur. Polym. J. 2013. V. 49. P. 3302–3308. https://doi.org/10.1016/j.eurpolymj.2013.07.003
  9. Faizuloev E., Marova A., Nikonova A., Volkova I., Gorshkova M., Izumrudov V. // Carbohydr. Polym. 2012. V. 89. № 4. P. 1088–1094
  10. Wan A., Xu Q., Yan Sun Y., Li H. // J. Agric. Food Chem. 2013. V. 61. P. 6921–6928. https://doi.org/10.1021/jf402242e
  11. Gruškienė R., Deveikytė R., Makuška R. // Chemija. 2013. V. 24. № 4. P. 325–334.
  12. Belalia R., Grelier S., Benaissa M., Coma V. // J. Agric. Food Chem. 2008. V. 56. P. 1582. https://doi.org/10.1021/jf071717
  13. Dormard A., Rinaudo M., Terrassin C. // Int. J. Biol. Macromol. 1986. V. 8. P. 105–107.
  14. Makuska R., Gorochovceva N. // Carbohydr. Polym. 2006. V. 64. № 2. P. 319–327.
  15. Holappa J., Nevalainen T., Savolainen J., Soininen P., Elomaa M., Safin R., Suvanto S., Pakkanen T., Masson M., Loftsson T., Järvinen T. // Macromolecules. 2004. V. 37. № 4. P. 2784–2789.
  16. Lim S. H., Hudson S. M. // Carbohydr. Res. 2004. V. 339. № 2. P. 313–319.
  17. Olins D. E., Olins F. L., von Hippel P. H. // J. Mol. Biol. 1967. V. 24. № 2. P. 157–176. https://doi.org/10.1016/0022-2836(67)90324-5
  18. Cai G., Jiang H., Tu K., Wang L., Zhu K. // Macromol. Biosci. 2009. V. 9. P. 256–261. https://doi.org/10.1002/mabi.200800153
  19. Loubaki E., Sicsic S., Le Goffic F. // Eur. Polym. J. 1989. V. 25. P. 379–384.
  20. Беллами И. Новые данные по ИК-спектрам сложных молекул. М: Мир, 1971. 318 с.
  21. Nakanishi Von K. Infrared Absorption Spectroscopy. Tokio: Verlag Holden-Day, Inc., San Francisco und Nankodo Co. 1962.
  22. Леви Г., Нельсон Г. Руководство по ЯМР 13С для химиков-органиков. М.: Мир, 1975.
  23. Le Roy F., Jolnson, Jankowski W. G. Carbon 13C-NMR Spectra. New York; London; Sidney, Toronto: Wiley, 1972.

Supplementary files

Supplementary Files
Action
1. JATS XML
Download
2. Fig. 1. Scheme of two-stage synthesis of mHTZ.

Download (167KB)
Indexing metadata
3. Fig. 2. Optical density at 450 nm of aqueous solutions of N-mCTZ (1), mCTZ 1 (2), mCTZ 3 (3) samples in media with different pH values.

Download (78KB)
Indexing metadata
4. Fig. 3. IR Fourier spectra of samples of CTZ (1), N-mCTZ (2), mCTZ 1 (3).

Download (800KB)
Indexing metadata
5. Fig. 4. Potentiometric titration curves of samples of N-mCTZ (1), mCTZ 1 (2), mCTZ 3 (3), and initial CTZ (4).

Download (656KB)
Indexing metadata
6. Fig. 5. 13C NMR spectra of modified products N-mCTZ (a), mCTZ 1 (b) and mCTZ 3 (c) in D2O.

Download (351KB)
Indexing metadata
7. Fig. 6. Particle sizes of polyplexes obtained with different ratios of mCTZ/DNA components (phosphate buffer, pH 7.4): 1 — N-mCTZ; 2 — mCTZ 1.

Download (738KB)
Indexing metadata
8. Fig. 7. Particle sizes of polyplexes with the composition mCTZ/DNA = 8:1 in phosphate buffer solutions with pH 7.4 at different concentrations of NaCl salt: 1 — N-mCTZ/DNA, 2 — mCTZ 1/DNA.

Download (716KB)
Indexing metadata

Copyright (c) 2024 Russian Academy of Sciences