Abstract
We have investigated thein 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 PALA-containing liposomal formulations using distearoylphosphatidylcholine (DSPC), distearoylphosphatidylglycerol (DSPG), and polyethyleneglycol-derivatized distearoylphosphatidylethanolamine (PEG-DSPE) were made and their cytotoxicity was measured. In 72 hr continuous exposure experiment with C-26 cells, the 50% growth inhibitory concentration (IC50) of DSPG-PALA liposome formulation was 0.09 μM, which showed about 65-fold more potent than unencapsulated free PALA (5.1 μM). Similar degree of increase in cytotoxicity was also observed in 1 hr exposure experiment. However, the IC50 of PEG-DSPE-PALA liposome and DSPC-PALA liposome were 10.7 μM and 11.8 μM, respectively, which showed slightly less potent than unencapsulated free PALA. Physical characteristics of PALA-liposomes, such as the size and drug:lipid ratio were also determined. In conclusion, negatively-charged DSPG-PALA liposome showed the highest cytotoxic effect among tested on the C-26 cellsin vitro.
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Kim, JS., Heath, T.D. In vitro cytotoxic effect ofN-(phosphonacetyl)-L-aspartic acid in liposome against C-26 murine colon carcinoma. Arch Pharm Res 23, 167–171 (2000). https://doi.org/10.1007/BF02975508
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DOI: https://doi.org/10.1007/BF02975508