Article

Projet
 
Annabelle GEZE, Denis WOUESSIDJEWE, Luc CHOISNARD,   
Titre
Self-assembled biotransesterified cyclodextrins as potential Artemisinin nanocarriers. II: In vitro behavior toward the immune system and in vivo biodistribution assessment of unloaded nanoparticles  
[Full paper ]
Auteurs
J. B.G. Yaméogo, A. Gèze, L. Choisnard, J-L Putaux, R. Mazet, C. Passirani, M. Keramidas, J-L Coll, N. Lautram, J. Bejaud, R. Semdé, D. Wouessidjewe
Edition
European Journal of pharmaceutics and biopharmaceutics, 88, 683-694
Année
2014
Résumé
In a previous study, we reported on the formulation of Artemisinin-loaded surface-decorated nanoparticles (nanospheres and nanoreservoirs) by co-nanoprecipitation of PEG derivatives (PEG1500 and PEG4000-stearate, polysorbate 80) and biosynthesized c-CD fatty esters. In the present study, the co-nanoprecipitation was extended to the use of a PEGylated phospholipid, namely DMPE-PEG2000. As our goal was to prepare long-circulating nanocarriers for further systemic delivery of Artemisinin (ART), here, we have investigated, on the one hand, the in vitro behavior of these surface-modified c-CD-C10particles toward the immune system (complement activation and macrophage uptake assays) and, on the other hand, their biodistribution features in mice. These experiments showed that the in vitro plasma protein adsorption and phagocytosis by macrophage cells triggered by c-CD-C10nanoparticles were significantly reduced when their surface was decorated with amphiphilic PEGylated molecules, in particular PEG1500-stearate, DMPE-mPEG2000 or polysorbate 80. The prolonged blood circulation time assessed by fluorescence imaging was demonstrated for unloaded c-CD-C10-based nanospheres and nanoreservoir particles containing DMPE-PEG2000 and polysorbate 80, respectively. These nanoparticles also proved to be non-hemolytic at the concentration range used in vivo. Within the limits of the con-ducted experiments, the co-nanoprecipitation technique may be considered as an alternative for surface modification of amphiphilic CD-based drug delivery systems and may be applied to the systemic delivery of ART.