ArticleArthritis research & therapy2010
Development of a macromolecular prodrug for the treatment of inflammatory arthritis: mechanisms involved in arthrotropism and sustained therapeutic efficacy.
Article in Arthritis research & therapy, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 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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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
27 citing papers in PubMed, 69 citations in OpenAlex.
- Neural Inflammation in Thoracic Dorsal Root Ganglia Mediates Cardiopulmonary Spinal Afferent Sensitization in Chronic Heart Failure.bioRxiv : the preprint server for biology · 2025Article
- siRNA conjugate with high albumin affinity and degradation resistance for delivery and treatment of arthritis in mice and guinea pigs.Nature biomedical engineering · 2025Article
- Glucocorticoids-based prodrug design: Current strategies and research progress.Asian journal of pharmaceutical sciences · 2024Review
- Prodrug-based nanomedicines for rheumatoid arthritis.Discover nano · 2024Review
- Diflunisal-loaded poly(propylene sulfide) nanoparticles decrease S. aureus-mediated bone destruction during osteomyelitis.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2021Article
- Structural optimization of HPMA copolymer-based dexamethasone prodrug for improved treatment of inflammatory arthritis.Journal of controlled release : official journal of the Controlled Release Society · 2020Article
- Polymer-drug conjugate therapeutics: advances, insights and prospects.Nature reviews. Drug discovery · 2019Review
- The Development of a Macromolecular Analgesic for Arthritic Pain.Molecular pharmaceutics · 2019Article
- Enhanced Therapeutic Effect of RGD-Modified Polymeric Micelles Loaded With Low-Dose Methotrexate and Nimesulide on Rheumatoid Arthritis.Theranostics · 2019Article
- Co-Delivery of Prednisolone and Curcumin in Human Serum Albumin Nanoparticles for Effective Treatment of Rheumatoid Arthritis.International journal of nanomedicine · 2019Article
- HPMA-Copolymer Nanocarrier Targets Tumor-Associated Macrophages in Primary and Metastatic Breast Cancer.Molecular cancer therapeutics · 2017Article
- Novel Drug Delivery Systems Tailored for Improved Administration of Glucocorticoids.International journal of molecular sciences · 2017Review
- Acid-Sensitive Sheddable PEGylated, Mannose-Modified Nanoparticles Increase the Delivery of Betamethasone to Chronic Inflammation Sites in a Mouse Model.Molecular pharmaceutics · 2017Article
- Dexamethasone-(C21-phosphoramide)-[anti-EGFR]: molecular design, synthetic organic chemistry reactions, and antineoplastic cytotoxic potency against pulmonary adenocarcinoma (A549).Drug design, development and therapy · 2016Article
- The Evaluation of the Therapeutic Efficacy and Side Effects of a Macromolecular Dexamethasone Prodrug in the Collagen-Induced Arthritis Mouse Model.Pharmaceutical research · 2016Article
- A review of UHMWPE wear-induced osteolysis: the role for early detection of the immune response.Bone research · 2016Review
- Trojan horses and guided missiles: targeted therapies in the war on arthritis.Nature reviews. Rheumatology · 2015Review
- Benefits and risks of low-dose glucocorticoid treatment in the patient with rheumatoid arthritis.Rheumatology (Oxford, England) · 2014Review
- Macromolecular therapeutics.Journal of controlled release : official journal of the Controlled Release Society · 2014Review
- Early diagnosis of orthopedic implant failure using macromolecular imaging agents.Pharmaceutical research · 2014Article
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 1 country.
Funding
Abstract
introductionThe purpose of the present manuscript is to test the hypothesis that arthrotropic localization and synovial cell internalization account for the unique capacity of N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-dexamethasone conjugate (P-Dex, a macromolecular prodrug of dexamethasone) to induce sustained amelioration of joint inflammation and inhibition of tissue damage in an animal model of inflammatory arthritis.
methodsRats with adjuvant-induced arthritis (AA) were treated with P-Dex, free dexamethasone, saline or HPMA homopolymer. To define the biodistribution of P-Dex, conjugates with different imaging labels were given to AA rats and analyzed. Isolated joint tissues were evaluated by fluorescence-activated cell sorting (FACS) and immunohistochemical staining. Cellular uptake of P-Dex and its effects on apoptosis and production of proinflammatory cytokines were examined using human monocyte-macrophages and fibroblasts.
resultsA single systemic administration of P-Dex completely suppressed AA for >20 days. Magnetic resonance imaging demonstrated higher HPMA copolymer influx into the inflamed joints than the normal joints. Immunohistochemistry and FACS analyses of arthritic joints revealed extensive uptake of the polymer conjugate by synovial fibroblasts and myeloid lineage cells. The capacity of P-Dex to suppress inflammation was confirmed in monocyte-macrophage cultures in which P-Dex treatment resulted in suppression of lipopolysaccharide-induced IL-6 and TNFα release. Similarly, TNFα-induced expression of matrix metalloproteinases (MMP1 and MMP3) in synovial fibroblasts from a rheumatoid arthritis patient was suppressed by P-Dex. P-Dex showed no detectable effect on monocyte apoptosis.
conclusionsP-Dex provides superior and sustained amelioration of AA compared with an equivalent dose of free dexamethasone. The arthrotropism and local retention of P-Dex is attributed to the enhanced vascular permeability in arthritic joints and the internalization of P-Dex by synovial cells. The uptake and processing of P-Dex by macrophages and fibroblasts, and downregulation of proinflammatory mediators, provides an explanation for the sustained anti-inflammatory efficacy of P-Dex in this model of inflammatory arthritis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.