pH-sensitive liposomes as a carrier for oligonucleotides: a physico-chemical study of the interaction between DOPE and a 15-mer oligonucleotide in quasi-anhydrous samples.
pH-sensitive liposomes made of dioleoylphosphatidylethanolamine (DOPE)/oleic acid (OA)/cholesterol (CHOL) mixtures were shown to be very promising carriers for oligonucleotides (ON). However, it appeared necessary to clarify the structural consequence of the interactions of ON with the liposome, and especially on DOPE, the lipid responsible for the pH sensitivity. The present study was carried out by differential scanning calorimetry and X-ray diffraction, at low hydration. In such a case, DOPE generally adopt a hexagonal phase. It could be shown that ON increased DOPE transition temperature and increased v/al, as a result of electrostatic interactions between ON and DOPE headgroups. OA was found to have exactly opposite effects, its presence between DOPE molecules inhibiting the formation of hydrogen bonds. The presence of both ON and OA allowed the system to organize in a lamellar phase below the solid/liquid transition, whereas above this temperature ON preferably interacted with DOPE in a hexagonal phase and led OA to separate.
URA CNRS 1218, Physico-chimie-Pharmacotechnie-Biopharmacie, Université Paris 11, Centre d'Etudes Pharmaceutiques, 5 rue Jean Baptiste Clément, 92296 Châtenay-Malabry Cedex, France.
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De Oliveira
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Fattal
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Couvreur
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Lesieur
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Bourgaux
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Ollivon
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Dubernet
D002152:Calorimetry, Differential Scanning; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002784:Cholesterol / Q000737:chemistry; D004337:Drug Carriers; D006860:Hydrogen Bonding; D006863:Hydrogen-Ion Concentration; D008081:Liposomes / Q000737:chemistry*; D019301:Oleic Acid / Q000737:chemistry; D009841:Oligonucleotides / Q000737:chemistry*; D010714:Phosphatidylethanolamines / Q000737:chemistry*; D055672:Static Electricity; D013696:Temperature; D013816:Thermodynamics; D014961:X-Ray Diffraction
D004337:Drug Carriers; D008081:Liposomes; D009841:Oligonucleotides; D010714:Phosphatidylethanolamines; C094877:dioleoyl phosphatidylethanolamine; D019301:Oleic Acid; D002784:Cholesterol