Chromatography of functionalized liposomes and their components.

The antitumour drug 1-beta-D-arabinofuranosylcytosine (ara C) was acylated by means of oleic acid anhydride, resulting in the prodrug N4-oleoyl-ara C. Together with a lipophilic biotin derivative, this lipophilic prodrug was incorporated into the bilayer membrane of unilamellar liposomes prepared by means of the detergent dialysis method. On addition of these biotinylated prodrug-liposomes to an excess of avidin, biotin residues were complexed with avidin. The unreacted avidin was removed by chromatography on the Ultrogel AcA-22 column. The prodrug-liposome-avidin complex was coupled to biotinylated monoclonal antibodies through the free binding sites of the immobilized avidin. Unreacted antibodies were removed by chromatography on an Ultrogel AcA-22 column. In vitro, the liposome-antibody complexes selectively bound to cells which were recognized by the monoclonal antibodies linked to the liposomes. For this reason, a promising strategy towards a specific chemotherapy of cancer is expected.