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Liposomal Drug with Carnosine and Lipoic Acid: Preparation, Antioxidant and Antiplatelet Properties

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Abstract

The conditions for producing phosphatidylcholine liposomes containing lipoic acid and carnosine together were determined. The obtained liposomes are 180–250-nm spherical particles with an efficiency of lipoic acid inclusion of 50–70% (for carnosine, 17–33%). Based on the model of the oxidation of phosphatidylcholine by hydrogen peroxide, an antioxidant effect of carnosine, lipoic acid or lipoic acid with carnosine together was demonstrated; it consisted in inhibition of lipid peroxidation process, which was manifested in a decrease in the formation of lipid peroxidation products that react with thiobarbituric acid. It was established that lipoic acid (5 mM) and carnosine (0.1–10 mM) in liposomes exhibit an antioxidant effect. At the same time, it was demonstrated that the content of the appropriate lipid peroxidation products in liposomes with antioxidants (lipoic acid + carnosine) was 15 times lower than in control liposomes (without antioxidants). The effect of the obtained liposomal drugs on the platelet aggregation induced by arachidonic acid was evaluated. It was found that the liposomal drug containing lipoic acid (1.5 mM) and carnosine (2.1 mM) inhibited platelet aggregation by 50–55% relative to the control (platelets and arachidonic acid), while liposomes without antioxidants and water-soluble forms of carnosine and lipoic acid had almost no effect on platelet aggregation caused by arachidonic acid.

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ACKNOWLEDGMENTS

The authors are grateful to Abduldzhabbar Balsam Tarek for obtaining liposomal drugs; to the head of Representative office of LIPOID AG Company (Germany) in Moscow Candidate of Chemistry A.V. Symon for providing phosphatidylcholine Lipoid S-100; to Doctor of Biology, Professor of Pirogov Russian National Research Medical University (Ministry of Health of Russian Federation) Yu.O. Teselkin for valuable comments and assistance in writing this article.

Funding

This work was carried out as a part of the State tasks of Pirogov Russian National Research Medical University (State registration no. AAAA-A19-100390063-9) and Research Center of Neurology (State registration no. AAAA-A19-119111290050-6).

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Correspondence to V. A. Shchelkonogov.

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Statement of Compliance with Standards of Research involving Humans as Subjects

All procedures performed in the study involving human participants were in accordance with the ethical standards of the 1964 Helsinki Declaration and its later amendments. Informed consent for taking biomaterial was obtained from all individual participants involved in the study.

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Translated by A. Barkhash

Abbreviations: LA, lipoic acid; AA, arachidonic acid; DPPC, dipalmitoylphosphatidylcholine; PC, phosphatidylcholine; EI, efficiency of inclusion; TBA-AP, thiobarbituric acid-active products.

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Shchelkonogov, V.A., Darnotuk, E.S., Chekanov, A.V. et al. Liposomal Drug with Carnosine and Lipoic Acid: Preparation, Antioxidant and Antiplatelet Properties. BIOPHYSICS 66, 278–285 (2021). https://doi.org/10.1134/S0006350921020214

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  • DOI: https://doi.org/10.1134/S0006350921020214

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