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Comparative Pharmacokinetics and Biodistribution of Etoposide in a Polymer Dosage Form and as Free Drug Substance

  • N. V. GukasovaEmail author
  • I. A. Tubasheva
  • S. L. Kuznetsov
  • A. I. Murav’eva
  • S. V. Aleshin
  • V. V. Sokolov
  • T. A. Antipova
  • E. A. Vorontsov
Article

A polymer dosage form of etoposide (PFE) was obtained as submicron particles based on the copolymer of lactic and glycolic acids (PLGA). Pharmacokinetics and biodistributions of etoposide in rat blood and organs after a single i.p. injection of the polymeric form and etoposide drug substance at doses of 10 mg/kg (of active ingredient) were compared and showed that absorption and elimination of etoposide from rat organs slowed if the PFE was used. The increases of T1/2 and MRT and decreases of Kel, Cmax/AUC(0 – 48), and Cl were indicative of this. Liver and lungs had the greatest tissue availability (ft) for the PFE. Etoposide accumulation in tumor tissue was studied after a single i.p. injection of PFE and etoposide drug substance at doses of 25 mg/kg to mice with grafted Ca755 murine breast adenocarcinoma. The etoposide distribution coefficient between blood and tumor tissue after 1 and 24 h was greater for the PFE, indicating the accumulation of etoposide in tumor tissue was greater if the PFE was used.

Keywords

etoposide copolymer of lactic and glycolic acids pharmacokinetics tissue availability biodistribution. 

Notes

Acknowledgments

The work was sponsored by Contract No. 14.604.21.0072 on the topic “Production technology development for polymer drug dosage forms for cancer therapy” in the framework of FTP “Research and development on science and technology priority directions for 2014 – 2020.” The unique identifier for the applied research (project) is RFMEFI60414X0072.

References

  1. 1.
    J. A. Sinkule, Pharmacotherapy, 4(2), 61 – 73 (1984).CrossRefGoogle Scholar
  2. 2.
    D. H. Johnson, F. A. Greco, J. Strupp, et al., J. Clin. Oncol., 8(10), 1613 – 1617 (1990).CrossRefGoogle Scholar
  3. 3.
    K. R. Hande, Eur. J. Cancer, 34(10), 1514 – 1521 (1998).CrossRefGoogle Scholar
  4. 4.
    W. Y. Qian, D. M. Sun, R. R. Zhu, et al., Int. J. Nanomed., 7, 5781 – 5792 (2012).Google Scholar
  5. 5.
    R. Saadati, S. Dadashzadeh, Z. Abbasian, et al., Pharm. Res., 30(4), 985 – 995 (2013).CrossRefGoogle Scholar
  6. 6.
    J. Yordanov, R. Skrobanska, and A. Evangelatov, Colloids Surf., B, 101, 215 – 222 (2013).CrossRefGoogle Scholar
  7. 7.
    M. Snehalatha, K. Venugopal, R. N. Saha, et al., Drug Delivery, 15(5), 277 – 287 (2008).CrossRefGoogle Scholar
  8. 8.
    Z. Wang, Z. Li, D. Zhang, et al., Drug Delivery, 22(1), 79 – 85 (2015).CrossRefGoogle Scholar
  9. 9.
    S. Jun, C. Yi, M. Fangli, et al., in: Abstracts of the International Conference on Biomedical Engineering and Biotechnology, Macao (2012); DOI:  https://doi.org/10.1109/iCBEB.2012.312.
  10. 10.
    A. I. Murav’eva, E. A. Vorontsov, N. V. Gukasova, et al., Ross. Nanotekhnol., 11(3 – 4), 84 – 91 (2016).Google Scholar
  11. 11.
    Handbook for Preclinical Drug Trials [in Russian], Part 1, Grif i K, Moscow (2012).Google Scholar
  12. 12.
    G. A. Posypanova, L. B. Gorshkova, A. V. Rodina, et al., Khim.-farm. Zh., 50(8), 45 – 49 (2016); Pharm. Chem. J., 50(8), 543 – 547 (2016).Google Scholar
  13. 13.
    M. C. Pigatto, D. L. Mossmann, and T. Dalla Costa, Biomed. Chromatogr., 29(4), 529 – 536 (2015).CrossRefGoogle Scholar
  14. 14.
    A. Kumari, S. K. Yadav, and S. C. Yadav, Colloids Surf., B, 75(1), 1 – 18 (2010).CrossRefGoogle Scholar
  15. 15.
    T. Musumeci, C. A. Venturab, I. Giannone, et al., Int. J. Pharm., 325(1 – 2), 172 – 179 (2006).CrossRefGoogle Scholar
  16. 16.
    J. H. Park, S. Kwon, M. Lee, H. Chunga, et al., Biomaterials, 27, 119 – 126 (2006).CrossRefGoogle Scholar
  17. 17.
    L. H. Reddya, R. K. Sharma, K. Chuttani, et al., J. Controlled Release, 105(3), 185 – 198 (2005).CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • N. V. Gukasova
    • 1
    Email author
  • I. A. Tubasheva
    • 1
  • S. L. Kuznetsov
    • 1
  • A. I. Murav’eva
    • 1
  • S. V. Aleshin
    • 1
  • V. V. Sokolov
    • 2
  • T. A. Antipova
    • 3
  • E. A. Vorontsov
    • 1
  1. 1.National Research Center Kurchatov InstituteMoscowRussia
  2. 2.N. I. Vavilov Institute of General GeneticsRussian Academy of SciencesMoscowRussia
  3. 3.Russian Research Center for Molecular Diagnostics and TherapyMoscowRussia

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