The effect of lipid derivative of anti-tumor drug sarcolysin embedded in phospholipid nanoparticles in the experiments in vivo

Tereshkina Yu.A.1 , Torkhovskaya T.I.1, Sanzhakov M.A.1, Kostryukova L.V.1, Khudoklinova Yu.Yu.1, Tikhonova E.G.1

1. Institute of Biomedical Chemistry, Moscow, Russia
Section: Experimental Study
DOI: 10.18097/PBMC20216706491      PubMed Id: 34964443
Year: 2021  Volume: 67  Issue: 6  Pages: 491-499
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 in size (“Sarcolysin-NP”). The effect of the resulting composition was investigated in vivo in comparison with the free substance of sarcolysin. The composition intravenous administration to mice showed an improvement in the pharmacokinetic parameters of sarcolysin associated with its initial higher (by 22%) level in the blood and prolonged circulation, which was also observed in mice with P388 tumor. In mice with three types of tumors — lymphocytic leukemia P388, lymphocytic leukemia L1210, and adenocarcinoma of the mammary gland Ca755 — administration of two doses of sarcolysin over a period of 7 days showed its predominant antitumor effect. The maximum tumor growth inhibition was noted for lymphocytic leukemia L1210 and adenocarcinoma of the mouse mammary gland Ca755 (at a dose of Sarcolysin-NP — 8,4 mg/kg), which was higher in comparison with free substance by more than 24% and 17%, respectively. Differences in the life span of the treated animals were revealed significantly at a dose of 10 mg/kg and amounted to 25% and 17,4% for lymphocytic leukemia P388 and L1210, respectively, and 11% for adenocarcinoma Ca755. In an experiment on rats, acute toxicity of Sarcolysin-NP administered intravenously showed that an average LD50 value 2-3 times exceeded a similar parameter for commercial preparations of free sarcolysin (Melphalan and Alkeran), which indicates its lower toxicity.
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Keywords: sarcolysin, lipid derivative, phospholipid nanoparticles, oncology, myeloma

Tereshkina, Yu. A., Torkhovskaya, T. I., Sanzhakov, M. A., Kostryukova, L. V., Khudoklinova, Yu. Yu., Tikhonova, E. G. (2021). The effect of lipid derivative of anti-tumor drug sarcolysin embedded in phospholipid nanoparticles in the experiments in vivo. Biomeditsinskaya Khimiya, 67(6), 491-499.
This paper is also available as the English translation: 10.1134/S1990750822020093
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