1. The mode of dexamethasone decoration influences avidin-nucleic-acid-nano-assembly organ biodistribution and in vivo drug persistence
- Author
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Giovanni Ribaudo, Alberto Ongaro, Martina Bruna Violatto, Elisa Gnodi, Paolo Bigini, Donatella Barisani, Pietro Invernizzi, Isabella Pellerani, Marco Carbone, Elisabetta Casarin, Mario Salmona, Alice Passoni, Elisa Schiavon, Margherita Morpurgo, Gloria Marchini, Andrea Mattarei, Ongaro, A, Violatto, M, Casarin, E, Pellerani, I, Marchini, G, Ribaudo, G, Salmona, M, Carbone, M, Passoni, A, Gnodi, E, Schiavon, E, Mattarei, A, Barisani, D, Invernizzi, P, Bigini, P, and Morpurgo, M
- Subjects
Biodistribution ,medicine.medical_treatment ,Biomedical Engineering ,Pharmaceutical Science ,Medicine (miscellaneous) ,Bioengineering ,Dexamethasone ,Polyethylene Glycols ,Steroid ,Mice ,Pharmacokinetics ,In vivo ,Nucleic Acids ,PEG ratio ,medicine ,Animals ,Tissue Distribution ,General Materials Science ,Liver targeting ,biology ,Chemistry ,BIO/13 - BIOLOGIA APPLICATA ,Avidin ,In vitro ,Nanomedicine ,ANANAS ,Autoimmune liver disease ,Liver disease ,Nucleic acid ,Biophysics ,biology.protein ,Nanoparticles ,Molecular Medicine - Abstract
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.
- Published
- 2022
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