Article

Projet
 
Denis WOUESSIDJEWE, Annabelle GEZE, Luc CHOISNARD, Delphine LEVILLY, Véronique BLANC-MARQUIS,   
Titre
Biodistribution and preliminary toxicity studies of nanoparticles made of Biotransesterified β–cyclodextrins and PEGylated phospholipids  
[Full paper ]
Auteurs
P. Perret, S. Bacot, A. Gèze, A. Gentil Dit Maurin, M. Debiossat, A. Soubies, V. Blanc-Marquis, L. Choisnard, J. Boutonnat, C. Ghezzi, J.L. Putaux, C. Lancelon-Pin, L.M. Riou,⁎, D. Wouessidjewe
Edition
Materials Science & Engineering C 2018, 85, 7-17
Année
2018
Résumé
Background: The modification of β-cyclodextrins (βCDs) by grafting alkyl chains on the primary and/or secondary face yields derivatives (βCD-C10) able to self-organize under nanoprecipitating conditions into nanoparticles (βCD-C10-NP) potentially useful for drug delivery. The co-nanoprecipitation of βCD-C10 with polyethylene glycol (PEG) chains yields PEGylated NPs (βCD-C10-PEG-NP) with potentially improved stealthiness. The objectives of the present study were to characterize the in vivo biodistribution of βCD-C10-PEG-NP with PEG chain length of 2000 and 5000 Da using nuclear imaging, and to preliminarily evaluate the in vivo acute and extended acute toxicity of the most suitable system. Research design and methods: The in vivo and ex vivo biodistribution features of naked and decorated nanoparticles were investigated over time following intravenous injection of 125I-radiolabeled nanoparticles to mice. The potential toxicity of PEGylated βCD-C10 nanosuspensions was evaluated in a preliminary in vivo toxicity study involving blood assays and tissue histology following repeated intraperitoneal injections of nanoparticles to healthy mice. Results: The results indicated that βCD-C10-PEG5000-NP presented increased stealthiness with decreased in vivo elimination and increased blood kinetics without inducing blood, kidney, spleen, and liver acute and extended acute toxicity. Conclusions: βCD-C10-PEG5000-NPs are stealth and safe systems with potential for drug delivery.