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Head-to-head comparative pharmacokinetic and biodistribution (PK/BD) study of two dexamethasone prodrug nanomedicines on lupus-prone NZB/WF1 mice
- Source :
- Nanomedicine
- Publication Year :
- 2020
-
Abstract
- HPMA copolymer-based dexamethasone prodrug (P-Dex) and PEG-based dexamethasone prodrug (PEG-Dex, ZSJ-0228) were previously found to passively target the inflamed kidney and provide potent and sustained resolution of nephritis in NZB/WF1 lupus-prone mice. While both prodrug nanomedicines effectively ameliorate lupus nephritis, they have demonstrated distinctively different safety profiles. To explore the underlining mechanisms of these differences, we conducted a head-to-head comparative PK/BD study of P-Dex and PEG-Dex on NZB/WF1 mice. Overall, the systemic organ/tissue exposures to P-Dex and Dex released from P-Dex were found to be significantly higher than those of PEG-Dex. The high prodrug concentrations were sustained in kidney for only 24 h, which cannot explain their lasting therapeutic efficacy (>1 month). P-Dex showed sustained presence in liver, spleen and adrenal gland, while the presence of PEG-Dex in these organs was transient. This difference in PK/BD profiles may explain PEG-Dex’ superior safety than P-Dex.
- Subjects :
- Biodistribution
endocrine system
Adenosine
Polymers
Biomedical Engineering
Lupus nephritis
Pharmaceutical Science
Medicine (miscellaneous)
Bioengineering
Spleen
02 engineering and technology
Pharmacology
Kidney
Dexamethasone
Article
03 medical and health sciences
Mice
Pharmacokinetics
medicine
polycyclic compounds
Animals
Humans
General Materials Science
Prodrugs
Tissue Distribution
030304 developmental biology
0303 health sciences
Systemic lupus erythematosus
Mice, Inbred NZB
business.industry
Prodrug
021001 nanoscience & nanotechnology
medicine.disease
Lupus Nephritis
Disease Models, Animal
medicine.anatomical_structure
Nanomedicine
Molecular Medicine
Nanoparticles
0210 nano-technology
business
Nephritis
hormones, hormone substitutes, and hormone antagonists
medicine.drug
Subjects
Details
- ISSN :
- 15499642
- Volume :
- 29
- Database :
- OpenAIRE
- Journal :
- Nanomedicine : nanotechnology, biology, and medicine
- Accession number :
- edsair.doi.dedup.....da026a80c2c452928736c06dc19a9945