The mode of dexamethasone decoration influences avidin-nucleic-acid-nano-assembly organ biodistribution and in vivo drug persistence.


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
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

102497

Informations de copyright

Copyright © 2021 Elsevier Inc. All rights reserved.

Auteurs

Alberto Ongaro (A)

Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy.

Martina Bruna Violatto (MB)

Department of Biochemistry and Molecular Pharmacology, Istituto di Ricerche Farmacologiche "Mario Negri" IRCCS, Milano, Italy.

Elisabetta Casarin (E)

ANANAS Nanotech S.r.l., Padova, Italy.

Isabella Pellerani (I)

Department of Biochemistry and Molecular Pharmacology, Istituto di Ricerche Farmacologiche "Mario Negri" IRCCS, Milano, Italy.

Gloria Marchini (G)

Department of Biochemistry and Molecular Pharmacology, Istituto di Ricerche Farmacologiche "Mario Negri" IRCCS, Milano, Italy.

Giovanni Ribaudo (G)

Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy.

Mario Salmona (M)

Department of Biochemistry and Molecular Pharmacology, Istituto di Ricerche Farmacologiche "Mario Negri" IRCCS, Milano, Italy.

Marco Carbone (M)

Division of Gastroenterology and Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), San Gerardo Hospital, Monza, Italy; International Center for Digestive Diseases.

Alice Passoni (A)

Department of Environmental Health Sciences, Istituto di Ricerche Farmacologiche "Mario Negri" IRCCS, Milano, Italy.

Elisa Gnodi (E)

Division of Gastroenterology and Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy; International Center for Digestive Diseases.

Elisa Schiavon (E)

Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy.

Andrea Mattarei (A)

Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy.

Donatella Barisani (D)

Division of Gastroenterology and Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy; International Center for Digestive Diseases.

Pietro Invernizzi (P)

Division of Gastroenterology and Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), San Gerardo Hospital, Monza, Italy; International Center for Digestive Diseases.

Paolo Bigini (P)

Department of Biochemistry and Molecular Pharmacology, Istituto di Ricerche Farmacologiche "Mario Negri" IRCCS, Milano, Italy.

Margherita Morpurgo (M)

Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy; CRIBI Biotechnology Cente, University of Padova, Padova, Italy. Electronic address: margherita.morpurgo@unipd.it.

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Classifications MeSH