The mode of dexamethasone decoration influences avidin-nucleic-acid-nano-assembly organ biodistribution and in vivo drug persistence.
ANANAS
Autoimmune liver disease
Dexamethasone
Liver disease
Liver targeting
Nanomedicine
Journal
Nanomedicine : nanotechnology, biology, and medicine
ISSN: 1549-9642
Titre abrégé: Nanomedicine
Pays: United States
ID NLM: 101233142
Informations de publication
Date de publication:
02 2022
02 2022
Historique:
received:
16
07
2021
revised:
28
10
2021
accepted:
01
11
2021
pubmed:
29
11
2021
medline:
8
4
2022
entrez:
28
11
2021
Statut:
ppublish
Résumé
Avidin-Nucleic-Acid-NanoASsemblies (ANANAS) possess natural tropism for the liver and, when loaded with dexamethasone, reduce clinical progression in an autoimmune hepatitis murine model. Here, we investigated the linker chemistry (hydrazide-hydrazone, Hz-Hz, or carbamate hydrazide-hydrazone, Cb-Hz bond) and length (long, 5 kDa PEG, or short, 5-6 carbons) in biotin-dexamethasone conjugates used for nanoparticle decoration through in vitro and in vivo studies. All four newly synthesized conjugates released the drug at acidic pH only. In vitro, the Hz-Hz and the PEG derivatives were less stable than the Cb-Hz and the short chain ones, respectively. Once injected in healthy mice, dexamethasone location in the PEGylated ANANAS outer layer favors liver penetration and resident macrophages uptake, while drug Hz-Hz, but not Cb-Hz, short spacing prolongs drug availability. In conclusion, the tight modulation of ANANAS decoration can significantly influence the host interaction, paving the way for the development of steroid nanoformulations suitable for different pharmacokinetic profiles.
Identifiants
pubmed: 34838993
pii: S1549-9634(21)00140-4
doi: 10.1016/j.nano.2021.102497
pii:
doi:
Substances chimiques
Nucleic Acids
0
Avidin
1405-69-2
Polyethylene Glycols
3WJQ0SDW1A
Dexamethasone
7S5I7G3JQL
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
102497Informations de copyright
Copyright © 2021 Elsevier Inc. All rights reserved.