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, Résumé: L'idée directrice de ce travail de thèse était d'introduire au sein de mésophases lipidiques des molécules de ?-cyclodextrine (?CD) amphiphiles obtenue par bio-estérification afin d'obtenir des nano-assemblages plurimoléculaires et multi-compartimentés combinant trois fonctions essentielles pour le transport ou la vectorisation de molécules thérapeutiques : (i) la capacité d'incorporer une substance d'intérêt par formation de complexe d'inclusion avec la cyclodextrine
, dont l'action biologique soit différente de celle assurée par la première substance. L'ensemble des travaux ont porté sur le dérivé ?CD-C10 polysubstitué en face secondaire par des chaînes hydrocarbonées en C10 avec un degré moyen de substitution de 7,3. L'association de ce dérivé avec trois catégories de lipides a été envisagée : des tensioactifs micellaires non-ioniques (Brij 98, Polysorbate 80, n-dodécyl-?, D-maltoside), un lipide lyotrope non lamellaire formant des mésophases de type cubique bicontinue (monooléine)
, Selon une démarche principalement physico-chimique, différentes techniques ont été mises en oeuvre pour caractériser les systèmes mixtes lipide/?CD-C10 aux échelles moléculaire et supramoléculaire : diffusion-diffraction des rayons X, calorimétrie différentielle, spectrophotométrie d'absorption UV-visible, spectroscopie de fluorescence, diffusion de la lumière statique (turbidimétrie) ou quasi-élastique
, L'ensemble des résultats démontrent que le dérivé ?CD-C10 forme spontanément ou selon un protocole très simple, des assemblages plurimoléculaires mixtes avec les trois catégories de lipides, assemblages dont la topologie dépend de la structure chimique du lipide et du taux de cyclodextrine amphiphile incorporé (tubules, vésicules uni-ou oligolamellaires, cubosomes). Ces assemblages sont stables et capables d'incorporer une substance hôte hydrophobe, notamment les vésicules mixtes tensioactif non-ionique/ ?CD-C10 et les cubosomes mixtes monooléine/P80/ ?CD-C10
, Mots clés : Cyclodextrines amphiphiles, lipides lyotropes, mésophases lipidiques, tensioactifs non ioniques, agrégats supramoléculaires, auto-assemblages mixtes
, Laboratoire de rattachement : UMR CNRS 8612-Institut Galien Paris-Sud Laboratoire de Physico-Chimie des Systèmes Polyphasés 5 rue Jean-Baptiste Clément
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, Pôle : Pharmacotechnie et Physico-Chimie Pharmaceutique Université Paris-Sud 11
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