Biomedical Chemistry: Research and Methods 2019, 2(3), e00098

Preparation and Properties of Antitumor Drug Based on Lipid Derivative of Sarcolysin

Yu.A. Tereshkina1*, M.A. Sanzhakov1, L.V. Kostryukova1, E.I. Korotkevich1, A.A. Chistov1,2, E.G. Tikhonova1,
V.N. Prozorovsky1, O.M. Ipatova1

1Institute of Biomedical Chemistry, 10 Pogodinskaya str., Moscow, 119121 Russia; *e-mail: burova13@gmail.com
2Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences,
16/10, bld.7 Miklukho-Maklay, Moscow, 117198 Russia

Keywords: sarcolysin; lipid derivative; phospholipid nanoparticles; oncology

DOI: 10.18097/BMCRM00098

The whole version of this paper is available in Russian.

The conditions for the preparation of a drug formulations based on the lipid derivative of sarcolysin embedded in phospholipid nanoparticles have been optimized. The drug is an ultra-thin emulsion with a light transmittance above 80% and a particle size of not more than 50 nm. It should be noted that 99% of the lipid derivative of sarcolysin are incorporated into phospholipid nanoparticles. Preservation of aggregation stability in the aquatic environment was observed for at least 2 days. In vitro experiments have shown that sarcolysin, introduced as a part of phospholipid nanoparticles, is distributed among lipoproteins and protein components of plasma. Moreover, the content of sarcolysin in all fractions involved in the transport of biologically active substances in the body, is significantly higher in case of prodrug administration (lipid derivative of sarcolysin) in the composition of phospholipid nanoparticles than, as compared with administration of a free form (pharmacological substances) to the incubation medium. The transformation of a prodrug into the drug sarcolysin occurs in the blood cells.
Figure 1. The mechanism of the damaging effect of chloroethylamines on [4].

Figure 2. General reaction scheme for the synthesis of the lipid derivative sarcolysin with decanol.

Figure 3. Light transmission of a drug sample at a wavelength of 660 nm.

Figure 4. Particle size distribution in the volume of the drug sample.

Figure 5. Chromatogram of an analysis of a drug suspension on the content of a lipid derivative of sarcolysin in it by LC / MS.

Figure 6. The content of sarcolysin in the fractions of lipoproteins and delipidated fraction of blood plasma when administered as part of «Sarcolysin-NPh» (dark columns) and in free form (light columns).

Figure 7. Dynamics of changes in the content of lipid derivative of sarcolysin (LDS) in blood components of experimental animals after the addition of Sarcolysin-NPh ((100±5) mg/ml of LDS): A – in whole blood (the spread of indications did not exceed 5% and is comparable to the size of the symbol in the figure); B – in plasma and blood form elements (BFE).

Figure 8. The change in the content of sarcolysin lipid derivative after the addition of Sarcolysin-NPh (squares) and sarcolysin in whole blood after the addition of Sarcolysin-NPh (white triangles) and sarcolysin-substance (black triangles).

Figure 9. Changes in the content of sarcolysin in plasma (A) and blood form elements (B) after adding to the whole blood Sarcolysin-NPh (white symbols) and sarcolysin (black symbols).

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Table 1. Characteristics of emulsion samples obtained at various technological parameters.

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Table 2. The change in particle diameter in a unimodal distribution, polydispersity index and light transmission at a wavelength of 660 nm in samples of drug emulsion.

FUNDING

The work was financially supported by the Ministry of Education and Science of the Russian Federation, under the State Contract № 14.N08.11.1029 «Preclinical studies of a drug based on a lipid derivative of sarcolysin in a liposomal form for the treatment of myeloma and hemoblastosis».

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