2. Academic Validation
  3. Dexamethasone prodrug nanomedicine (ZSJ-0228) treatment significantly reduces lupus nephritis in mice without measurable side effects - A 5-month study

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

  • Nanomedicine. 2021 Jan:31:102302. doi: 10.1016/j.nano.2020.102302.
Zhifeng Zhao 1,  Zhenshan Jia 1,  Kirk W Foster 2,  Xin Wei 1,  Fangfang Qiao 1,  Haochen Jiang 1,  Yan Jin 1,  Guojuan Li 1,  Ningrong Chen 1,  Gang Zhao 1,  Geoffrey M Thiele 3,  Jennifer L Medlin 4,  James R O'Dell 3,  Dong Wang 5
Affiliations

Affiliations

  • 1 Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE.
  • 2 Department of Pathology and Microbiology, College of Medicine, University of Nebraska Medical Center, Omaha, NE.
  • 3 Division of Rheumatology and Immunology, Department of Internal Medicine, College of Medicine, University of Nebraska Medical Center, Omaha, NE; Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE, USA.
  • 4 Division of Rheumatology and Immunology, Department of Internal Medicine, College of Medicine, University of Nebraska Medical Center, Omaha, NE.
  • 5 Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE. Electronic address: dwang@unmc.edu.
PMID: 32980548 DOI: 10.1016/j.nano.2020.102302
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.

Keywords

Dexamethasone; Lupus nephritis; Nanomedicine; Prodrug; Side effects; ZSJ-0228.

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