PHYSICAL-PROPERTIES AND PHARMACOLOGICAL ACTIVITY IN-VITRO AND IN-VIVOOF OPTIMIZED LIPOSOMES PREPARED FROM A NEW CANCEROSTATIC ALKYLPHOSPHOLIPID

Liposomes from tadecyl-(1,1-dimethyl-4-piperidino-4-yl)-phosphate (OPP ), a new alkylphospholipid derivative with an improved cancerostatic a ctivity, were prepared for the first time and the activity in vitro an d in vivo was characterised. The formation of liposomes (MLV, SUV and LUVET) differing in cholesterol content, charge, and sterical stabilis ation is possible without serious problems, despite the lysolipid-like structure of the OPP. Liposomes with a low amount of cholesterol and with PEG(2000)DSPE-coating were the most stable OPP liposomes, both in buffer and in serum. The cytotoxicity of micellar or liposomal OPP ag ainst breast cancer cell lines in vitro was in the range of 20-60 mu M . The cytotoxicity of the liposomal formulation was inversely related to the content of cholesterol, whereas the sterical stabilisation and/ or the incorporation of a positive charge had only a very moderate mod ulating effect on the inhibition of cell proliferation. The strongest antitumour effect on the xenotransplanted breast cancer MT-3 in vivo w as obtained with sterically stabilised OPP liposomes with low CH conte nt. The beneficial therapeutic effect of these liposomes was accompani ed by better tolerance and a significant inhibition of haemolysis comp ared to micellar OPP. (C) 1998 Elsevier Science B.V. All rights reserv ed.