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

Autor: Annabelle Gèze, Christine Lancelon-Pin, V. Blanc-Marquis, Laurent Riou, A. Gentil Dit Maurin, Jean-Luc Putaux, Pascale Perret, Audrey Soubies, Luc Choisnard, Catherine Ghezzi, Denis Wouessidjewe, Marlène Debiossat, Sandrine Bacot, J. Boutonnat
Přispěvatelé: Radiopharmaceutiques biocliniques (LRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Département de pharmacochimie moléculaire (DPM ), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Univ. Grenoble Alpes, CNRS, CHU Grenoble Alpes, Grenoble INP*, TIMC-IMAG, Grenoble, France, Centre de Recherches sur les Macromolécules Végétales (CERMAV ), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Thérapeutique Recombinante Expérimentale (TIMC-IMAG-TheREx), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Centre Hospitalier Universitaire [Grenoble] (CHU), Perret, Pascale
Jazyk: angličtina
Rok vydání: 2018
Předmět:
0301 basic medicine
Biodistribution
Materials science
PEGylated amphiphiles
Bioengineering
Toxicity studies
02 engineering and technology
Polyethylene glycol
[SDV.IB.MN]Life Sciences [q-bio]/Bioengineering/Nuclear medicine
Pharmacology
complex mixtures
Polyethylene Glycols
[SDV.IB.MN] Life Sciences [q-bio]/Bioengineering/Nuclear medicine
Biomaterials
Mice
03 medical and health sciences
chemistry.chemical_compound
Imaging
Three-Dimensional
In vivo
PEG ratio
Toxicity Tests
Acute
Animals
Tissue Distribution
Colloids
Phospholipids
ComputingMilieux_MISCELLANEOUS
Drug Carriers
Esterification
beta-Cyclodextrins
Organ Size
021001 nanoscience & nanotechnology
Acute toxicity
3. Good health
030104 developmental biology
[CHIM.POLY]Chemical Sciences/Polymers
chemistry
Mechanics of Materials
Bioesterified β-cyclodextrins
Creatinine
Toxicity
Drug delivery
Nanoparticles
Female
lipids (amino acids
peptides
and proteins)
0210 nano-technology
Ex vivo
Zdroj: Materials Science and Engineering: C
Materials Science and Engineering: C, Elsevier, 2018, 85, pp.7-17. ⟨10.1016/j.msec.2017.12.017⟩
Materials Science and Engineering: C, 2018, 85, pp.7-17. ⟨10.1016/j.msec.2017.12.017⟩
ISSN: 0928-4931
DOI: 10.1016/j.msec.2017.12.017⟩
Popis: 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.
Databáze: OpenAIRE
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