Oligonucleotide delivery by a cationic derivative of the polyene antibiotic amphotericin B - II: study of the interactions of the oligonucleotide/cationic vector complexes with lipid monolayers and lipid unilamellar vesicles

We report a study of the behavior of oligodeoxyribonucleotide (ODN)/amphote ricin B3-(N'-dimethylamino)propylamide (AMA) complexes, in the presence of lipid monolayers and large unilamellar vesicles. This study follows the rec ent discovery of the capacity of AMA, as a new cationic vector? to enhance ODN cellular uptake and efficacy. It aims at investigating the internalizat ion mode of a nucleic acid by AMA. A first study at the air-water interface of AMA and AMA/ODN by surface pressure measurement shows that only free AM A would adsorb at the air-water interface. Second, in the presence of zwitt erionic phospholipid- and sterol-containing mixture? ODN-AMA interactions i n solution would be higher than lipid-AMA interactions at the interface. In monolayer or with large unilamellar vesicles, AMA monomers adsorb mainly a t the phospholipid interface. These results favor a crossing mechanism thro ugh AMA channel formation, despite the size of ODN, (C) 2000 Elsevier Scien ce B.V. All rights reserved.