In vitro cytotoxic effect of N-(phosphonacetyl)-L-aspartic acid in liposome against C-26 murine colon carcinoma

We have investigated the in vitro cytotoxic effect of liposome-encapsulated N-(phosphonacetyl)-L-aspartic acid (PALA) against C-26 murine colon cancer cells, and have compared it in this regard to free PALA. Three different P ALA-containing liposomal formulations using distearoylphosphatidylcholine ( DSPC), distearoylphosphatidylglycerol (DSPG), and polyethyleneglycol-deriva tized distearoylphosphatidylethanolamine (PEG-DSPE) were made and their cyt otoxicity was measured. In 72 hr continuous exposure experiment with C-26 c ells, the 50% growth inhibitory concentration (IC50) of DSPG-PALA liposome formulation was 0.09 mu M, which showed about 65-fold more potent than unen capsulated free PALA (5.1 mu M). Similar degree of increase in cytotoxicity was also observed in 1 hr exposure experiment. However, the IC50 of PEG-DS PE-PALA liposome and DSPC-PALA liposome were 10.7 mu M and 11.8 mu M, respe ctively, which showed slightly less potent than unencapsulated free PALA. P hysical characteristics of PALA-liposomes, such as the size and drug:lipid ratio were also determined. In conclusion, negatively-charged DSPG-PALA lip osome showed the highest cytotoxic effect among tested on the C-26 cells in vitro.