Polymeric dexamethasone prodrugs attenuate lupus nephritis in MRL/lpr mice with reduced glucocorticoid toxicity.
Dexamethasone
Glucocorticoids
Lupus nephritis
Polymeric prodrug
Toxicity
Journal
Nanomedicine : nanotechnology, biology, and medicine
ISSN: 1549-9642
Titre abrégé: Nanomedicine
Pays: United States
ID NLM: 101233142
Informations de publication
Date de publication:
08 2022
08 2022
Historique:
received:
14
01
2022
revised:
10
05
2022
accepted:
14
06
2022
pubmed:
30
6
2022
medline:
3
9
2022
entrez:
29
6
2022
Statut:
ppublish
Résumé
Due to their potent immunosuppressive and anti-inflammatory effects, glucocorticoids (GCs) are the most widely used medications in treating lupus nephritis (LN). Long-term use of GCs, however, is associated with numerous off-target adverse effects. To reduce GCs' adverse effects, we previously developed two polymeric dexamethasone prodrug nanomedicines: N-(2-hydroxypropyl) methacrylamide (HPMA) copolymer-based dexamethasone prodrug (P-Dex), and micelle-forming polyethylene glycol (PEG)-based dexamethasone prodrug (ZSJ-0228). Both P-Dex and ZSJ-0228 provided sustained amelioration of LN in lupus-prone NZB/W F1 mice with reduced GC-associated adverse effects. Here, we have extended our investigation to the MRL/lpr mouse model of LN. Compared to dose equivalent daily dexamethasone sodium phosphate (Dex) treatment, monthly P-Dex or ZSJ-0228 treatments were more effective in reducing proteinuria and extending the lifespan of MRL/lpr mice. Unlike the daily Dex treatment, ZSJ-0228 was not associated with measurable GC-associated adverse effects. In contrast, adrenal gland atrophy was observed in P-Dex treated mice.
Identifiants
pubmed: 35768036
pii: S1549-9634(22)00065-X
doi: 10.1016/j.nano.2022.102579
pmc: PMC9427713
mid: NIHMS1827790
pii:
doi:
Substances chimiques
Glucocorticoids
0
Polymers
0
Prodrugs
0
Dexamethasone
7S5I7G3JQL
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
102579Subventions
Organisme : NIAID NIH HHS
ID : R01 AI119090
Pays : United States
Informations de copyright
Copyright © 2022 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest Dong Wang and Zhenshan Jia are co-inventors of the patent (PCT/US16/61728), which covers the ZSJ-0228 prodrug technology. Dong Wang is a co-founder of Shannon Pharmaceuticals, which has licensed the ZSJ-0228 technology for commercial development and provides funding for Chemistry Manufacturing and Controls studies in Dong Wang's laboratory. Steven R. Goldring and Mary K. Crow are paid consultants for Shannon Pharmaceuticals.
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