Polymeric dexamethasone prodrugs attenuate lupus nephritis in MRL/lpr mice with reduced glucocorticoid toxicity

Zhifeng Zhao, Haochen Jiang, Xiaoke Xu, Zhenshan Jia, Rongguo Ren, Kirk W. Foster, Xin Wei, Ningrong Chen, Steven R. Goldring, Mary K. Crow, Dong Wang

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Article number102579
JournalNanomedicine: Nanotechnology, Biology, and Medicine
Volume44
DOIs
StatePublished - Aug 2022

Keywords

  • Dexamethasone
  • Glucocorticoids
  • Lupus nephritis
  • Polymeric prodrug
  • Toxicity

ASJC Scopus subject areas

  • Bioengineering
  • Medicine (miscellaneous)
  • Molecular Medicine
  • Biomedical Engineering
  • Materials Science(all)
  • Pharmaceutical Science

Fingerprint

Dive into the research topics of 'Polymeric dexamethasone prodrugs attenuate lupus nephritis in MRL/lpr mice with reduced glucocorticoid toxicity'. Together they form a unique fingerprint.

Cite this