![Development of Liposomes Based on a Pyrrolo[3,2-L]Acridinone Derivative and Assessment of Their Antitumor Activity in Leukosis](/upload/iblock/0d1/osm2lkw3eydvedwwflasbdu3nwudjtqo.jpg "Development of Liposomes Based on a Pyrrolo[3,2-L]Acridinone Derivative and Assessment of Their Antitumor Activity in Leukosis")
Key words: acridinone; liposomes; cytotoxic activity; lyophilization; cryoprotectant.
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The chemical structure of acridine contains ring-shaped nitrogen atoms, which determine its numerous biological and chemical properties. The scientific community considers the effects of acridine and its derivatives on tumors of various origins to be of particular interest. Numerous publications report the synthesis and study of new compounds in this group, some of which have been shown to be more effective than 5-fluorouracil and cisplatin.
The aim of the study was to develop the liposomes based on pyrrolo[3,2-l]acridinone derivative Mob-155 S and study their antitumor activity regarding leukosis.
Materials and Methods. Acridinone liposomes were prepared using a thin-film method followed by lyophilization. Lactose, mannose, and sucrose were dissolved in the dispersion as cryoprotectants prior to lyophilization. Spectrophotometry, dynamic light scattering, and electrophoresis were used to obtain the qualitative and quantitative characteristics of the liposomes. Stability of the samples was monitored at two temperature conditions (6–8°C and 21–23°C). Cytotoxic activity was determined on a Jurkat line in comparison with the native Mob-155 S substance and the liposomes without the active compound.
Results. Immediately after production and during the short-term storage, Mob-155 S liposomes had the particles about 200 nm in size. After 40-day storage at 21–23°C, Mob-155 S concentration decreased, and there was an increase in the mean particle size up to 300–320 nm, and the polydispersity index up to 0.45–0.55. Experimental lyophilization with three types of saccharides was performed to improve stabilization. The marked protective effect manifested in the preservation of key quality liposome parameters was observed only under 10% mannose. In vitro studies demonstrated a significant reduction in tumor cell viability at relatively low concentrations of Mob-155 S.
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