Article

Projet
 
Denis WOUESSIDJEWEAnnabelle GEZELuc CHOISNARD,   
Titre
New nanoparticles obtained by co-​assembly of amphiphilic cyclodextrins and nonlamellar single-​chain lipids: Preparation and characterization  
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Auteurs
Nguyen, C-H ; Putaux, J-L; Santoni, G; Tfaili, S; Fourmentin, S; Coty, J-B; Choisnard, L; Geze, A; Wouessidjewe, D; Barratt, G; Lesieur, S; Legrand, F-X
Edition
Int. J. Pharm. 2017, 531(2), 444-456
Année
2017
Résumé
This work aimed at prepg. new nanoscale assemblies based on an amphiphilic bio-​esterified β-​cyclodextrin (β-​CD)​, substituted at the secondary face with n-​decanoic fatty acid chains (β-​CD-​C10)​, and monoolein (MO) as new carriers for parenteral drug delivery. Stable binary (β-​CD-​C10/MO) and ternary (β-​CD-​C10/MO​/stabilizer) nanoscale assemblies close to 100 nm in size were successfully prepd. in water by the solvent displacement method. The generated nanoparticles were fully characterized by dynamic light scattering, transmission electron microscopy, small-​angle X-​ray scattering, residual solvent anal., complement activation and the contribution of each formulation parameter was detd. by principal component anal. The β-​CD-​C10 units were shown to self-​organize into nanoparticles with a hexagonal supramol. packing that was significantly modulated by the molar ratio of the constituents and the presence of a steric or electrostatic stabilizer (DOPE-​PEG2000 or DOPA​/POPA, resp.)​. Indeed, nanoparticles differing in morphol. and in hexagonal lattice parameters were obtained while the co-​existence of multiple mesophases was obsd. in some formulations, in particular for the β-​CD-​C10/MO​/DOPA and β-​CD-​C10/MO​/POPA systems. The mixed β-​CD-​C10/MO​/DOPE-​PEG2000 nanoparticles (49:49:2 in mol​%) appeared to be the most suitable for use as a drug delivery system since they contained a very low amt. of residual solvent and showed a low level of complement C3 activation