title: In vitro cytotoxic effect of N-(phosphonacetyl)-L-aspartic acid in liposome against C-26 murine colon carcinoma.
abstract: 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 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 microM, which showed about 65-fold more potent than unencapsulated free PALA (5.1 microM). 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 microM and 11.8 microM, 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 cells in vitro.
authors.affiliation: College of Pharmacy, Sookmyung Women's University, Yongsan-Gu, Seoul, Korea. jskim@sdic.sookmyung.ac.kr
authors.forename: J S
authors.initials: JS
authors.lastname: Kim
authors.forename: T D
authors.initials: TD
authors.lastname: Heath
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001224:Aspartic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004337:Drug Carriers; D008081:Liposomes; D051379:Mice; D010316:Particle Size; D010746:Phosphonoacetic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D008081:Liposomes; D001224:Aspartic Acid; C013195:sparfosic acid; D010746:Phosphonoacetic Acid