MODIFIED POLYANIONIC POLYMERS FOR ENHANCED CELL-MEMBRANE INTERACTION

The affinity of poly(maleic acid-alt-2-cyclohexyl-1,3-dioxepin-5-ene) [poly(MA-CDA)] for cell membranes was improved by grafting hydrophobic groups onto the polymer. The membrane affinity of these modified polyanionic polymers was characterized by their interaction with negatively charged liposomes. The biological activity of the modified polymers in vitro was determined with cultured cell lines. The superoxide release from DMSO differentiated HL-60 cells, stimulated by the modified poly(MA-CDA), was remarkable compared to the unmodified poly(MA-CDA). This higher activity may be due to the improved affinity of the modified polymers for the cell membranes. The long-term cytotoxicity of the polymers was examined using J774 cells. It was observed that the polymers were cytotoxic at relatively high concentrations, and the cytotoxicity correlated with the improved membrane affinity. In both in vitro tests, the molecular weight of the modified poly(MA-CDA) affected the biological response. The higher activities were found for the lower molecular weight polymers.