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

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Abstract

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.

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Authors and Affiliations

  1. Moscow Technological University, M. V. Lomonosov Institute for Fine Chemical Technologies, 86 prosp. Vernadskogo, 119571, Moscow, Russian Federation, Russia

    E. D. Nikolskaya, M. R. Faustova, M. D. Mollaev & V. I. Shvets

  2. Russian Research Center for Molecular Diagnostics and Therapy, 8 Simpheropol’sky bulvar, 117149, Moscow, Russian Federation, Russia

    O. A. Zhunina, M. B. Sokol, N. G. Yabbarov & E. S. Severin

  3. National Research Center Kurchatov Institute, 1 pl. Akad. Kurchatova, 123182, Moscow, Russian Federation, Russia

    N. V. Gukasova

  4. N. N. Semenov Institute of Chemical Physics, Russian Academy of Sciences, 4 ul. Kosygina, 119991, Moscow, Russian Federation, Russia

    A. V. Lobanov

Authors
  1. E. D. Nikolskaya
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  2. M. R. Faustova
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  3. M. D. Mollaev
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  4. O. A. Zhunina
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  5. M. B. Sokol
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  6. N. G. Yabbarov
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  7. N. V. Gukasova
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  8. A. V. Lobanov
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  9. V. I. Shvets
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  10. E. S. Severin
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Corresponding authors

Correspondence to V. I. Shvets or E. S. Severin.

Additional information

Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 4, pp. 0747–0756, April, 2018.

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Nikolskaya, E.D., Faustova, M.R., Mollaev, M.D. et al. Development of a polymer system for the delivery of daunorubicin to tumor cells to overcome drug resistance. Russ Chem Bull 67, 747–756 (2018). https://doi.org/10.1007/s11172-018-2132-5

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  • DOI: https://doi.org/10.1007/s11172-018-2132-5

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