ArticleJournal of controlled release : official journal of the Controlled Release Society2014
Macromolecular prodrug of dexamethasone prevents particle-induced peri-implant osteolysis with reduced systemic side effects.
Article in Journal of controlled release : official journal of the Controlled Release Society, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 41 citations in OpenAlex.
- Arthrotomy-based preclinical models of particle-induced osteolysis: A systematic review.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2017Pooled it
- Supramolecular Zinc-Polyphenol Coordination Assemblies Mitigate Colonic Inflammation by Regulating Mucosal Barrier and Microbiome.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Targeted-delivery of nanomedicine-enabled methylprednisolone to injured spinal cord promotes neuroprotection and functional recovery after acute spinal cord injury in rats.Nanomedicine : nanotechnology, biology, and medicine · 2024Article
- Glucocorticoids-based prodrug design: Current strategies and research progress.Asian journal of pharmaceutical sciences · 2024Review
- Glucocorticoid Nanoparticles Show Full Therapeutic Efficacy in a Mouse Model of Acute Lung Injury and Concomitantly Reduce Adverse Effects.International journal of molecular sciences · 2023Article
- Dexamethasone Conjugates: Synthetic Approaches and Medical Prospects.Biomedicines · 2021Review
- Bioresponsive drug delivery systems for the treatment of inflammatory diseases.Journal of controlled release : official journal of the Controlled Release Society · 2020Review
- Anti-inflammatory drug-eluting implant model system to prevent wear particle-induced periprosthetic osteolysis.International journal of nanomedicine · 2019Article
- Discovery of biomarkers to identify peri-implant osteolysis before radiographic diagnosis.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2018Article
- Micelle-Forming Dexamethasone Prodrug Attenuates Nephritis in Lupus-Prone Mice without Apparent Glucocorticoid Side Effects.ACS nano · 2018Article
- Biomimetic and biodegradable cellulose acetate scaffolds loaded with dexamethasone for bone implants.Beilstein journal of nanotechnology · 2018Article
- Impaired resolution of DSS-induced colitis in mice lacking the glucocorticoid receptor in myeloid cells.PloS one · 2018Article
- Novel Drug Delivery Systems Tailored for Improved Administration of Glucocorticoids.International journal of molecular sciences · 2017Review
- Pharmacokinetic and Biodistribution Studies of HPMA Copolymer Conjugates in an Aseptic Implant Loosening Mouse Model.Molecular pharmaceutics · 2017Article
- The Evaluation of the Therapeutic Efficacy and Side Effects of a Macromolecular Dexamethasone Prodrug in the Collagen-Induced Arthritis Mouse Model.Pharmaceutical research · 2016Article
- RGD(F/S/V)-Dex: towards the development of novel, effective, and safe glucocorticoids.Drug design, development and therapy · 2016Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Aseptic implant loosening related to implant wear particle-induced inflammation is the most common cause of failure after joint replacement. Modulation of the inflammatory reaction to the wear products represents a rational approach for preventing aseptic implant failure. Long-term treatment using anti-inflammatory agents, however, can be associated with significant systemic side effects due to the drugs' lack of tissue specificity. To address this issue, N-(2-hydroxypropyl) methacrylamide (HPMA) copolymer-dexamethasone conjugate (P-Dex) was developed and evaluated for prevention of wear particle-induced osteolysis and the loss of fixation in a murine prosthesis failure model. Daily administration of free dexamethasone (Dex) was able to prevent wear particle-induced osteolysis, as assessed by micro-CT and histological analysis. Remarkably, monthly P-Dex administration (dose equivalent to free Dex treatment) was equally effective as free dexamethasone, but was not associated with systemic bone loss (a major adverse side effect of glucocorticoids). The reduced systemic toxicity of P-Dex is related to preferential targeting of the sites of wear particle-induced inflammation and its subcellular sequestration and retention by local inflammatory cell populations, resulting in sustained therapeutic action. These results demonstrate the feasibility of utilizing a macromolecular prodrug with reduced systemic toxicity to prevent wear particle-induced osteolysis.
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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.