Russian Chemical Bulletin

, Volume 67, Issue 4, pp 747–756 | Cite as

Development of a polymer system for the delivery of daunorubicin to tumor cells to overcome drug resistance

  • E. D. Nikolskaya
  • M. R. Faustova
  • M. D. Mollaev
  • O. A. Zhunina
  • M. B. Sokol
  • N. G. Yabbarov
  • N. V. Gukasova
  • A. V. Lobanov
  • V. I. Shvets
  • E. S. Severin
Full Article


Method for the synthesis of polymeric nanoparticles (NP) with encapsulated daunorubicin (DNR) was developed on the basis of double emulsion solvent evaporation technique using biodegradable poly(lactide-co-glycolide) (PLGA), which is aimed at customization of pharmacokinetic properties of the preparation, enhanced accumulation of DNR in tumor cells and prolongation of its action. The obtained polymer nanoparticles (DNR-PLGA) had average size ranging around 138±36 nm, with zeta-potential of –25.3 mV and the polydispersity index (PDI) of 0.072. The release kinetics of DNR from polymer nanoparticles at pH 7.4 and 5.0 has been studied. In vitro studies showed similar specific activity of DNR- PLGA in K562 and MCF-7 cancer cell lines together with an increase in activity in K562 Adr and MCF-7 Adr cell lines, which are anthracycline resistant, by 1.6 and 3.4 times. The study demonstrated the efficacy of the developed PLGA-based DNR delivery system in the improvement of antitumor effect of DNR, overcoming multidrug resistance in cancer cells, and also in the decrease in nonspecific toxicity of the preparation.

Key words

daunorubicin (DNR) poly(lactic-co-glycolic acid) (PLGA) polymeric nanoparticles (NP) release kinetics multidrug resistance (MDR) antitumor activity 


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  1. 1.
    M. B. Bychkov, E. K. Vosniy, A. M. Garin, V. A. Gorbunova, N. F. Orel, N. I. Perevodchikova, M. N. Preobrazhenskaya, M. B. Stenina, S. A. Tulyandin, Novye tsitostatiki v lechenii zlokachestvennykh opukholei [New Cytostatics in the Treatment of Malignant Tumors], RONTs im. N. N. Blokhina, Moscow, 1998, 128 pp. (in Russian).Google Scholar
  2. 2.
    O. Yu. Baranova, M. A. Volkova, Russ. Medical J. (Int. Ed.), 2001, 22 [Rus. Med. Zhurn., 2001, 22, 199] (in Russian).Google Scholar
  3. 3.
    A. V. Pivnik, Russ. Medical J. (Int. Ed.), 1999, 10 [Rus. Med. Zhurn., 1999, 10, 5] (in Russian).Google Scholar
  4. 4.
    A. L. A. Ferreira, L. S. Matsubara, B. B. Matsubara, Cardiovascular and Hematological Agents in Medicinal Chemistry, 2008, 4,278.CrossRefGoogle Scholar
  5. 5.
    I. V. Poddubnaya, Russ. Medical J. (Int. Ed.), 1998, 10 [Rus. Med. Zhurn., 1998, 10, 2] (in Russian).Google Scholar
  6. 6.
    E. S. Severin, A. V. Rodina, Uspekhi biol. Khimii, 2006, 46, 43 (in Russian).Google Scholar
  7. 7.
    P. Ma, R. J. Mumper, Nano Today, 2013, 8,313.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    J.-P. Gillet, T. Efferth, J. Remacle, Biochimica et Biophysica Acta (BBA)–Reviews on Cancer, 2007, 2,237.CrossRefGoogle Scholar
  9. 9.
    E. S. Severin, Russ. Chem. Rev., 2015, 84,43.CrossRefGoogle Scholar
  10. 10.
    D. Krajišnik, B. Čalija, N. Cekic, Formulation Challenges and Potential Benefits, 2017, 2,31.Google Scholar
  11. 11.
    K. V. Alekseev, I. N. Gritskova, S. A. Kedic, Polimery dlia farmatsevticheskoi tekhnologii [Polymers for Pharmaceutical Technology], SARMA, Moscow 2011, 511 pp. (in Russian).Google Scholar
  12. 12.
    R. Jalil, J. R. Nixon, J. Microencapsulation, 1990, 7,297.CrossRefPubMedGoogle Scholar
  13. 13.
    P. A. Gunatillake, R. Adhikari, Europuan Cells & Matherials, 2003, 5,1.CrossRefGoogle Scholar
  14. 14.
    CN Pat. 1973843.Google Scholar
  15. 15.
    J. Liu, Z. Qiu, S. Wang, L. Zhou, S. Zhang, Biomedical Materials, 2010, 5,1.Google Scholar
  16. 16.
    B. Han, B. Shen, Z. Wang, Polym. Adv. Technol., 2008, 9,36.CrossRefGoogle Scholar
  17. 17.
    P. P. G. Guimarães, M. F. Oloveira, A. D. M. Gomes, S. M. L. Gontijo, M. E. Cortés, P. P. Campos, C. T. R. Viana, S. P. Andrade, R D. Sinisterra, Colloids and Surfaces B: Biointerfaces, 2015, 136,248.CrossRefPubMedGoogle Scholar
  18. 18.
    K. Nan, F. Ma, H. Hou, W. R. Freeman, M. J. Sailor, L. Cheng, Acta Biomaterialia, 2014, 10, 3505.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    N. V. Gukasova, O. A. Zhunina, E. D. Nikolskaya, A. V. Pomazkov, M. A. Sapelkin, E. S. Severin, O. G. Tereshchenko, N. G. Yabbarov, FIPS application № 2016118302/15(028761) from 21.03.2017 (in Russian).Google Scholar
  20. 20.
    Y. Zhang, M. Huo, J. Zhou, A. Zou, W. Li, C. Yao, S. Xie, The AAPS J., 2010, 12,263.CrossRefPubMedGoogle Scholar
  21. 21.
    T. Mosmann, J. Immunol. Meth., 1983, 65,55.CrossRefGoogle Scholar
  22. 22.
    E. M. Treshchalina, O. S. Zukova, G. K. Gerasimova, N. V. Andronova, A. M. Garin, Metodicheskie ukazaniya po izuche niyu protivoopukholevoi aktivnosti farmakologicheskikh veshchestv. Rukovodstvo po eksperimental`nomu (doklinicheskomu) izucheniyu novykh farmakologicheskikh veshchestv [Guidelines for Examination of Antitumor Activity of Medicinal Compounds. Guidelines for Conduction of Preclinical Trial of New Medicinal Compounds], Medicina, 2005, 832 pp. (in Russian).Google Scholar
  23. 23.
    N. A. Peppas, Pharm. Acta Helv., 1985, 60,110.PubMedGoogle Scholar
  24. 24.
    M. Rahimi, H. Mobedi, A. Behnamghader, J. Micro encapsulation, 2016, 33,355.Google Scholar
  25. 25.
    T. G. Soni, J. U. Desai, C. D. Nagda, T. R. Gandhi, N. P. Chotai, Die Pharmazie Intern. J. Pharmaceutical Sci., 2008, 63, 31–34.Google Scholar
  26. 26.
    Y. Urasaki, T. Ueda, A. Yoshida, T. Fukushima, Anticancer Res., 1996, 16, 709.PubMedGoogle Scholar

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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • E. D. Nikolskaya
    • 1
  • M. R. Faustova
    • 1
  • M. D. Mollaev
    • 1
  • O. A. Zhunina
    • 2
  • M. B. Sokol
    • 2
  • N. G. Yabbarov
    • 2
  • N. V. Gukasova
    • 3
  • A. V. Lobanov
    • 4
  • V. I. Shvets
    • 1
  • E. S. Severin
    • 2
  1. 1.Moscow Technological UniversityM. V. Lomonosov Institute for Fine Chemical TechnologiesMoscow, Russian FederationRussia
  2. 2.Russian Research Center for Molecular Diagnostics and TherapyMoscow, Russian FederationRussia
  3. 3.National Research Center Kurchatov InstituteMoscow, Russian FederationRussia
  4. 4.N. N. Semenov Institute of Chemical PhysicsRussian Academy of SciencesMoscow, Russian FederationRussia

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