Enhanced cytotoxicity of doxorubicin encapsulated in liposomes with reconstituted Sendai F-proteins

Sendai F-virosomes, a novel type of liposome with reconstituted Sendai F-pr oteins, have been tested as a delivery system for various bioactive materia ls. However, encapsulation limitations and difficulties in controlling thei r constituents were drawbacks for further application to therapeutic purpos es. We have tried to control virosomal constituents and have enhanced drug encapsulation efficiency into the virosomes. In vitro cytotoxicity of doxor ubicin encapsulated in the F-virosomes were compared with free doxorubicin and doxorubicin in conventional liposomes. The F-virosomes were spontaneous ly prepared by detergent dialysis, a reconstitution process of Sendai F-pro teins into liposomes. The reconstitution density of F-proteins affected the vesicle size of virosomes prepared by detergent dialysis; the larger amoun t of F-proteins made a smaller size of virosomes. There was little variatio n of size with time at physiological conditions, whilst the vesicle size of virosomes increased at acidic storage conditions (pH 5.5). Doxorubicin enc apsulated in the F-virosomes exhibited a lower IC50 against B16BL6 mouse me lanoma cells and Chang human hepatocarcinoma cells than that in conventiona l liposomes. The F-virosomes also exhibited higher cellular uptake than con ventional liposomes. Addition of dioleoylphophatidylethanolamine, a fusogen ic phospholipid, into the F-virosome further increased the cellular uptake as well as in vitro cytotoxicity. These types of virosome formulations can be clinically applicable as versatile vesicles for the efficient delivery o f various therapeutic drugs, including genetic materials.