Dexamethasone prodrug nanomedicine (ZSJ-0228) treatment significantly reduces lupus nephritis in mice without measurable side effects — A 5-month study

Zhifeng Zhao, Zhenshan Jia, Kirk W. Foster, Xin Wei, Fangfang Qiao, Haochen Jiang, Yan Jin, Guojuan Li, Ningrong Chen, Gang Zhao, Geoffrey M. Thiele, Jennifer L. Medlin, James R. O'Dell, Dong Wang

Research output: Contribution to journalArticlepeer-review

Abstract

Lupus nephritis (LN) is a major cause of morbidity and mortality among systemic lupus erythematosus patients. Glucocorticoids (GCs) are uniformly used in clinical LN management. Their notorious toxicities, however, have hampered the long-term clinical application. To circumvent GC side effects while maintaining their potent therapeutic efficacy, we have developed a macromolecular prodrug nanomedicine based on dexamethasone (ZSJ-0228). The focus of this study was to investigate its long-term efficacy and, most importantly, safety in the lupus-prone NZB/W F1 mouse. Monthly ZSJ-0228 treatment for five months significantly reduced the incidence of nephritis in NZB/W F1 mice with an improved survival rate. In contrast to treatment with dose equivalent daily free dexamethasone, long-term monthly ZSJ-0228 did not result in any measurable GC-associated side effects. With its outstanding efficacy and exceptional safety, it is anticipated that ZSJ-0228 may be a novel therapy for long-term clinical management of LN.

Original languageEnglish (US)
Article number102302
JournalNanomedicine: Nanotechnology, Biology, and Medicine
Volume31
DOIs
StatePublished - Jan 2021

Keywords

  • Dexamethasone
  • Lupus nephritis
  • Nanomedicine
  • Prodrug
  • Side effects
  • ZSJ-0228

ASJC Scopus subject areas

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

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