Biodistribution and preliminary toxicity studies of nanoparticles made of Biotransesterified β-cyclodextrins and PEGylated phospholipids.

Autor: Perret P; INSERM, UMR 1039, Radiopharmaceutiques Biocliniques, Grenoble-Alpes University, France., Bacot S; INSERM, UMR 1039, Radiopharmaceutiques Biocliniques, Grenoble-Alpes University, France., Gèze A; DPM, UMR CNRS 5063, ICMG FR 2607, Faculty of Pharmacy, Grenoble-Alpes University, France., Gentil Dit Maurin A; DPM, UMR CNRS 5063, ICMG FR 2607, Faculty of Pharmacy, Grenoble-Alpes University, France., Debiossat M; INSERM, UMR 1039, Radiopharmaceutiques Biocliniques, Grenoble-Alpes University, France., Soubies A; INSERM, UMR 1039, Radiopharmaceutiques Biocliniques, Grenoble-Alpes University, France., Blanc-Marquis V; DPM, UMR CNRS 5063, ICMG FR 2607, Faculty of Pharmacy, Grenoble-Alpes University, France., Choisnard L; DPM, UMR CNRS 5063, ICMG FR 2607, Faculty of Pharmacy, Grenoble-Alpes University, France., Boutonnat J; CHU Grenoble-Alpes - TIMC UMR CNRS 5525, France., Ghezzi C; INSERM, UMR 1039, Radiopharmaceutiques Biocliniques, Grenoble-Alpes University, France., Putaux JL; CERMAV-CNRS, UPR 5301, ICMG FR 2607, Grenoble-Alpes University, France., Lancelon-Pin C; CERMAV-CNRS, UPR 5301, ICMG FR 2607, Grenoble-Alpes University, France., Riou LM; INSERM, UMR 1039, Radiopharmaceutiques Biocliniques, Grenoble-Alpes University, France. Electronic address: Laurent.Riou@univ-grenoble-alpes.fr., Wouessidjewe D; DPM, UMR CNRS 5063, ICMG FR 2607, Faculty of Pharmacy, Grenoble-Alpes University, France.
Jazyk: angličtina
Zdroj: Materials science & engineering. C, Materials for biological applications [Mater Sci Eng C Mater Biol Appl] 2018 Apr 01; Vol. 85, pp. 7-17. Date of Electronic Publication: 2017 Dec 15.
DOI: 10.1016/j.msec.2017.12.017
Abstrakt: 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 5000Da 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 125 I-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-PEG 5000 -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-PEG 5000 -NPs are stealth and safe systems with potential for drug delivery.
(Copyright © 2017 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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