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The Effect of Lipid Derivative of the Anti-Tumor Drug Sarcolysin Embedded in Phospholipid Nanoparticles in the Experiments in Vivo

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Abstract

In order to improve the therapeutic properties of the antitumor agent sarcolysin, we have previously developed and characterized a dosage form, representing its ester conjugate with decanol embedded in ultra-small phospholipid nanoparticles less than 30 nm (Sarcolysin-NPh). In this study we have compared the effect of this composition with free substance of sarcolysin in vivo. After the intravenous administration to mice, an improvement in the pharmacokinetic parameters of sarcolysin was associated with a higher (by 22%) initial level in the blood and with prolonged circulation. This was also observed in P388 tumor-bearing mice. At the same time, the amount and duration of the presence of sarcolysin in the tumor tissue were significantly higher (more than two times) when compared with the free substance. In mice with three types of tumors (lymphocytic leukemia P388, lymphocytic leukemia L1210, and mammary adenocarcinoma Ca755), a predominant antitumor effect was shown, which manifested itself in a significantly greater inhibition of tumor growth and an increase in the life span of animals. The maximum inhibition of tumor growth during treatment with Sarcolysin-NPh at a dose of 8.4 mg/kg was noted in the case of lymphocytic leukemia L1210 and mouse mammary adenocarcinoma Ca755 (more than 24% and 17% higher, respectively, in comparison with the substance). At a dose of 10 mg/kg, differences in the life expectancy of animals were higher by 25%, 17.4%, and 11% for lymphocytic leukemia P388, lymphocytic leukemia L1210, and adenocarcinoma Ca755, respectively. Sarcolysin-NPh intravenously to rats, demonstrated significantly lower acute toxicity than commercially available free Sarcolysin (Melphalan and Alkeran): the LD50 value for Sarcolysin-NPh was 2–3 times lower than that for free Sarcolysin. This indicates a lower toxicity of Sarcolysin-NPh.

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Funding

The work was performed within the framework of the Program for Basic Research in the Russian Federation for a long-term period (2021−2030) (no. 122030100170-5).

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Authors and Affiliations

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

    Yu. A. Tereshkina, T. I. Torkhovskaya, M. A. Sanzhakov, L. V. Kostryukova, Yu. Yu. Khudoklinova & E. G. Tikhonova

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  1. Yu. A. Tereshkina
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  2. T. I. Torkhovskaya
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  3. M. A. Sanzhakov
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  4. L. V. Kostryukova
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  5. Yu. Yu. Khudoklinova
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  6. E. G. Tikhonova
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Correspondence to Yu. A. Tereshkina.

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The authors declare that they have no conflict of interest. All animal experiments were performed in accordance with the National Standard of Russia 33044-2014 “Principles of Good Laboratory Practice.”

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Translated by A. Medvedev

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Tereshkina, Y.A., Torkhovskaya, T.I., Sanzhakov, M.A. et al. The Effect of Lipid Derivative of the Anti-Tumor Drug Sarcolysin Embedded in Phospholipid Nanoparticles in the Experiments in Vivo. Biochem. Moscow Suppl. Ser. B 16, 125–133 (2022). https://doi.org/10.1134/S1990750822020093

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  • DOI: https://doi.org/10.1134/S1990750822020093

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