The Development of a Macromolecular Dexamethasone Prodrug for the Treatment of Focal Segmental Glomerulosclerosis (FSGS)
Abstract
The overall purpose of the project is to develop a nephrotropic polyethylene glycol (PEG)-based dexamethasone (Dex) prodrug (PEG-Dex or ZSJ-0228) as an effective and safe therapy for focal segmental glomerulosclerosis (FSGS). During this funding period, we have identified the reason for the Adriamycin dose variation in FSGS mouse model induction as reported in the literature and have established a robust model establishment protocol. Using the Adriamycin-induced Balb/C mouse model of FSGS, we have confirmed the superior therapeutic efficacy and safety of a single dose i.v. administered PEG-Dex than dose equivalent Dex. Healthy mice and FSGS mice administered with Saline were used as the controls. Specifically, PEG-Dex treatment is significantly more effective than Dex in reducing proteinuria, ameliorating FSGS lesions, and restoring kidney functions. Multiple side effects, including abnormalities in bodyweight, blood glucose, liver functions, adrenal gland weight and lymphocyte counts were observed in Dex group, but not in PEG-Dex group. We have also synthesized PEG-Dex labeled with near-infrared dye IRDye 800CW and Alexa Fluor 647 for the studies planned for next year.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2023
- Accession Number
- AD1199738
Entities
People
- Dong Wang
Organizations
- University of Nebraska Medical Center