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)/amphotericin B3-(N'-dimethylamino)propylamide (AMA) complexes, in the presence of lipid monolayers and large unilamellar vesicles. This study follows the recent discovery of the capacity of AMA, as a new cationic vector, to enhance ODN cellular uptake and efficacy. It aims at investigating the internalization 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 AMA would adsorb at the air-water interface. Second, in the presence of zwitterionic phospholipid- and sterol-containing mixture, ODN-AMA interactions in solution would be higher than lipid-AMA interactions at the interface. In monolayer or with large unilamellar vesicles, AMA monomers adsorb mainly at the phospholipid interface. These results favor a crossing mechanism through AMA channel formation, despite the size of ODN.
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Laboratoire de Physicochimie Biomoléculaire et Cellulaire, CNRS ESA 7033, Université Pierre et Marie Curie, case 138, 4 place Jussieu, F-75252, Paris, France.
Saint-Pierre Chazalet
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D000666:Amphotericin B / Q000031:analogs & derivatives* / Q000737:chemistry; D000900:Anti-Bacterial Agents / Q000737:chemistry*; D002942:Circular Dichroism; D004121:Dimethyl Sulfoxide; D004337:Drug Carriers; D000431:Ethanol; D008563:Membrane Lipids / Q000737:chemistry*; D008854:Microscopy, Electron; D016376:Oligonucleotides, Antisense / Q000737:chemistry*; D010743:Phospholipids / Q000737:chemistry; D011312:Pressure; D012965:Sodium Chloride; D012996:Solutions
D000900:Anti-Bacterial Agents; D004337:Drug Carriers; D008563:Membrane Lipids; D016376:Oligonucleotides, Antisense; D010743:Phospholipids; D012996:Solutions; C408366:amphotericin B3-(N'-dimethylamino)propylamide; D000431:Ethanol; D012965:Sodium Chloride; D000666:Amphotericin B; D004121:Dimethyl Sulfoxide