ArticleArthritis and rheumatism2012
Dexamethasone prodrug treatment prevents nephritis in lupus-prone (NZB × NZW)F1 mice without causing systemic side effects.
Article in Arthritis and rheumatism, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
24 citing papers in PubMed, 46 citations in OpenAlex.
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- Glucocorticoids-based prodrug design: Current strategies and research progress.Asian journal of pharmaceutical sciences · 2024Review
- Single dose thermoresponsive dexamethasone prodrug completely mitigates joint pain for 15 weeks in a murine model of osteoarthritis.Nanomedicine : nanotechnology, biology, and medicine · 2024Article
- Macromolecular Dexamethasone Prodrug Ameliorates Neuroinflammation and Prevents Bone Loss Associated with Traumatic Brain Injury.Molecular pharmaceutics · 2022Article
- Polymeric dexamethasone prodrugs attenuate lupus nephritis in MRL/lpr mice with reduced glucocorticoid toxicity.Nanomedicine : nanotechnology, biology, and medicine · 2022Article
- Co-Delivery of Dexamethasone and Captopril by α8 Integrin Antibodies Modified Liposome-PLGA Nanoparticle Hybrids for Targeted Anti-Inflammatory/Anti-Fibrosis Therapy of Glomerulonephritis.International journal of nanomedicine · 2022Article
- Thermoresponsive polymeric dexamethasone prodrug for arthritis pain.Journal of controlled release : official journal of the Controlled Release Society · 2021Article
- Preclinical Dose-Escalation Study of ZSJ-0228, a Polymeric Dexamethasone Prodrug, in the Treatment of Murine Lupus Nephritis.Molecular pharmaceutics · 2021Article
- Dexamethasone Conjugates: Synthetic Approaches and Medical Prospects.Biomedicines · 2021Review
- Head-to-head comparative pharmacokinetic and biodistribution (PK/BD) study of two dexamethasone prodrug nanomedicines on lupus-prone NZB/WF1 mice.Nanomedicine : nanotechnology, biology, and medicine · 2020Article
- Genetically Engineered Human Kidney Cells for Real-Time Cytotoxicity Testing In Vitro.Molecular biotechnology · 2020Article
- CaBritish journal of pharmacology · 2019Article
- A Macromolecular Janus Kinase (JAK) Inhibitor Prodrug Effectively Ameliorates Dextran Sulfate Sodium-Induced Ulcerative Colitis in Mice.Pharmaceutical research · 2019Article
- Synthesis of budesonide conjugates and their anti-inflammatory effects: a preliminary study.Drug design, development and therapy · 2019Article
- Micelle-Forming Dexamethasone Prodrug Attenuates Nephritis in Lupus-Prone Mice without Apparent Glucocorticoid Side Effects.ACS nano · 2018Article
- Development of a Janus Kinase Inhibitor Prodrug for the Treatment of Rheumatoid Arthritis.Molecular pharmaceutics · 2018Article
- Pharmacokinetic and Biodistribution Studies of HPMA Copolymer Conjugates in an Aseptic Implant Loosening Mouse Model.Molecular pharmaceutics · 2017Article
- The Evaluation of Therapeutic Efficacy and Safety Profile of Simvastatin Prodrug Micelles in a Closed Fracture Mouse Model.Pharmaceutical research · 2016Article
- Simvastatin prodrug micelles target fracture and improve healing.Journal of controlled release : official journal of the Controlled Release Society · 2015Article
- Benefits and risks of low-dose glucocorticoid treatment in the patient with rheumatoid arthritis.Rheumatology (Oxford, England) · 2014Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
objectiveTo evaluate the potentially improved therapeutic efficacy and safety of nephrotropic macromolecular prodrugs of glucocorticoids (GCs) for the treatment of lupus nephritis.
methodsLupus-prone female (NZB × NZW)F1 mice received monthly injections of N-(2-hydroxypropyl) methacrylamide copolymer-based dexamethasone prodrug (P-Dex) or daily injections of dexamethasone phosphate sodium (Dex; overall dose equivalent to that of P-Dex) for 2 months. During treatment, the mice were monitored for albuminuria, mean arterial pressure, and serum autoantibody levels. Nephritis, renal immune complex levels, and macrophage infiltration were evaluated histologically. Bone quality was analyzed using peripheral dual x-ray absorptiometry and micro-computed tomography. The in vivo distribution of P-Dex was investigated using optical imaging, immunohistochemistry, and fluorescence-activated cell sorting (FACS). The antiinflammatory effect of P-Dex was validated using lipopolysaccharide-activated human proximal tubule epithelial (HK-2) cells.
resultsMonthly P-Dex injections completely abolished albuminuria in the (NZB × NZW)F1 mice; this approach was significantly more efficacious than daily Dex treatment. P-Dex treatment did not reduce serum levels of anti-double-stranded DNA antibodies or renal immune complexes but did decrease macrophage infiltration, which is a marker of chronic inflammation. Immunohistochemical and FACS analyses revealed that P-Dex was primarily sequestered by proximal tubule epithelial cells, and that it could attenuate the inflammatory response in HK-2 cell culture. In contrast to Dex treatment, P-Dex treatment did not lead to any significant deterioration of bone quality or reduction in the level of total serum IgG.
conclusionMacromolecularization of GCs renders them nephrotropic. Protracted retention, subcellular processing, and activation of GC prodrugs by kidney cells would potentiate nephritis resolution, with a reduced risk of systemic toxicities.
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Registered trials
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