Title: pH-sensitive liposomes with benzophenanthridine alkaloid sanguinarine and their cytotoxic activity

Authors: S.V. Lutsenko; S.N. Orekhov; N.E. Sedyakina; L.I. Salitrinnik; T.I. Gromovykh; N.B. Feldman

Addresses: Department of Biotechnology, Federal State Autonomous Educational Institution of Higher Education I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), 2-4 Bolshaya Pirogovskaya St., 119991 Moscow, Russia ' Department of Biotechnology, Federal State Autonomous Educational Institution of Higher Education I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), 2-4 Bolshaya Pirogovskaya St., 119991 Moscow, Russia ' Department of Biotechnology, Federal State Autonomous Educational Institution of Higher Education I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), 2-4 Bolshaya Pirogovskaya St., 119991 Moscow, Russia ' Department of Biotechnology, Federal State Autonomous Educational Institution of Higher Education I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), 2-4 Bolshaya Pirogovskaya St., 119991 Moscow, Russia ' Department of Biotechnology, Federal State Autonomous Educational Institution of Higher Education I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), 2-4 Bolshaya Pirogovskaya St., 119991 Moscow, Russia ' Department of Biotechnology, Federal State Autonomous Educational Institution of Higher Education I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), 2-4 Bolshaya Pirogovskaya St., 119991 Moscow, Russia

Abstract: The plant alkaloid sanguinarine has antitumour, antiangiogenic, antimicrobial and antiviral activity. However, the maximum manifestation of the therapeutic potential of sanguinarine is hindered by relatively low bioavailability and a number of side effects. To increase the bioavailability and effectiveness of the therapeutic effect, sanguinarine was introduced into the pH-sensitive liposomes by the remote loading method. The average diameter of liposome particles with sanguinarine was 107.4 ± 3.7 nm; the zeta potential -12.7 ± 1.5 mV. The effectiveness of the inclusion of sanguinarine in liposomes was 75.94 ± 2.18%. In the model experiments, the dynamics of the release of sanguinarine from liposomes was studied, and the prolonged release pattern was demonstrated. The cytotoxic activity (CTA) of liposomal sanguinarine against tumour cells of the MCF-7, HeLa and K 562 lines was studied in vitro. Liposomal sanguinarine exhibited a dose-dependent CTA for tumour cells of all the lines studied; the highest CTA was seen with HeLa cells (IC50 3.2 μM). For this cell line CTA of liposomal sanguinarine significantly (~2.2 times) exceeded the activity of the free drug. A comparative study of liposomal and free sanguinarine with respect to the ability to induce apoptosis of HeLa cells has also been performed. At a concentration of 5 μM the liposomal sanguinarine induced apoptosis in 41.96% of tumour cells, whereas the free sanguinarine - only in 20.32% of the cells. It is likely that the use of sanguinarine in the composition of pH-sensitive liposomes can promote its effective release from the acid medium of the endosomal compartment of tumour cells and the manifestation of a toxic effect. The presented data allow to consider liposomal sanguinarine as a promising antitumour agent.

Keywords: liposomes; pH-sensitive liposomes; sanguinarine; antitumour activity; apoptosis; cervical adenocarcinoma.

DOI: 10.1504/IJNT.2021.118158

International Journal of Nanotechnology, 2021 Vol.18 No.9/10, pp.823 - 832

Published online: 13 Oct 2021 *

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