Title: Preparation and investigation of in vitro cytotoxic activity of pH-sensitive liposomes with sanguinarine

Authors: S.V. Lutsenko; O.I. Gudkova; V.V. Kashirin; T.I. Gromovykh; N.B. Feldman

Addresses: 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 ' 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 ' 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 ' 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 ' 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: Sanguinarine is a benzophenanthridine alkaloid of plant origin showing antitumour, anti-inflammatory and a number of other activities. To increase the effectiveness of its therapeutic effect, sanguinarine was introduced into the pH-sensitive liposomes by the remote loading method using ammonium citrate. The average diameter of the obtained liposomes was equal to 144.8 ± 2.3 nm; zeta potential was equal to -16.3 ± 1.5 mV, the effectiveness of sanguinarine inclusion in liposomes was 68.7%. The release of sanguinarine from liposomes was prolonged; the lowest level of release was observed in a medium with a pH of 7.4, the highest at pH 5.5, which may be useful in preventing the release of the active substance in the blood stream and, conversely, in activating its release in the tumour growth zone. The cytotoxic activity of liposomal sanguinarine against cells of human squamous carcinoma A431 (IC50 9.5 μM) was significantly higher than its activity against the normal epidermal keratinocytes (NHEK) (IC50 25.1 μM). The drug also caused an effective dose-dependent induction of apoptosis in tumour cells of A431, while not affecting normal cells. Thus, liposomal sanguinarine can be considered as a promising antitumour agent acting on tumour cells by inducing apoptosis and exhibiting low cytotoxicity to normal human cells.

Keywords: sanguinarine; liposomes; ammonium citrate; bioavailability; drug release; cytotoxic activity; apoptosis.

DOI: 10.1504/IJNT.2019.102394

International Journal of Nanotechnology, 2019 Vol.16 No.1/2/3, pp.77 - 86

Published online: 12 Sep 2019 *

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