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The Increase of Anti-tuberculosis Efficacy of Rifampicin Incorporated Into Phospholipid Nanoparticles with Sodium Oleate

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Abstract—

A drug formulation of the anti-tuberculosis drug rifampicin, incorporated in nanoparticles (of 20–30 nm in diameter) from soy phosphatidylcholine with the addition of sodium oleate, has been developed in IBMC. Earlier, it demonstrated a higher bioavailability than the free drug substance. In this study we have shown higher anti-tuberculosis activity of this composition. In experiments performed on M. tuberculosis H37Rv cells, rifampicin in nanoparticles more actively inhibited cell growth than the free drug substance. The higher anti-tuberculosis activity was manifested by a 2-fold lower value of the minimum inhibitory concentration (MIC), 0.5 μg/mL, as compared to 1 μg/mL for free rifampicin. After treatment of mice with tuberculosis caused by the M. tuberculosis Erdman strain for 6 weeks with oral administration of rifampicin in nanoparticles (according to the prophylactic scheme, starting from day 3 after infection), the CFU value in the lungs was 22 times lower than after the same treatment with free rifampicin (1.7 units compared with 37.4 units). The LD50 value in mice was 2-fold higher for rifampicin in the nanocomposite due to protective action of nanoparticle phospholipids. In the context of the use of rifampicin, as an essential component of modern schemes of anti-tuberculosis therapy, the data obtained indicate the promise of the developed drug composition.

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Funding

This study was performed within the framework of the Program of Basic Scientific Research of the State Academies of Sciences for 2013–2020.

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Authors and Affiliations

  1. Institute of Biomedical Chemistry (IBMC), ul. Pogodinskaya 10, 119121, Moscow, Russia

    M. A. Sanzhakov, O. M. Ipatova, T. I. Torkhovskaya, E. G. Tikhonova, N. V. Medvedeva, T. S. Zakharova & V. N. Prozorovskiy

  2. Federal Research and Clinical Center of Physical-Chemical Medicine, ul. Malaya Pirogovskaya 1a, 119221, Moscow, Russia

    T. I. Torkhovskaya

  3. PLC IBMH-EcoBioPharm, Moscow, Russia

    E. G. Tikhonova

Authors
  1. M. A. Sanzhakov
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  2. O. M. Ipatova
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  3. T. I. Torkhovskaya
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  4. E. G. Tikhonova
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  5. N. V. Medvedeva
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  6. T. S. Zakharova
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  7. V. N. Prozorovskiy
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Corresponding author

Correspondence to T. I. Torkhovskaya.

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All animal experiments were carried out in accordance with the International Recommendations of the European Convention for the Protection of Vertebrate Animals used for experiments or for other scientific purposes (The European Convention, 1986).

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Translated by A. Medvedev

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Sanzhakov, M.A., Ipatova, O.M., Torkhovskaya, T.I. et al. The Increase of Anti-tuberculosis Efficacy of Rifampicin Incorporated Into Phospholipid Nanoparticles with Sodium Oleate. Biochem. Moscow Suppl. Ser. B 13, 271–276 (2019). https://doi.org/10.1134/S1990750819030077

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  • DOI: https://doi.org/10.1134/S1990750819030077

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