ArticlePharmaceutical research2018
Local Application of Pyrophosphorylated Simvastatin Prevents Experimental Periodontitis.
Article in Pharmaceutical research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
What it found
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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.
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.
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Who cites it
7 citing papers in PubMed, 13 citations in OpenAlex.
- Inhibitory impact of a mesoporous silica nanoparticle-based drug delivery system on Porphyromonas gingivalis-induced bone resorption.Journal of materials science. Materials in medicine · 2024Article
- Pharmacological Therapies for the Management of Inflammatory Bone Resorption in Periodontal Disease: A Review of Preclinical Studies.BioMed research international · 2022Review
- Thermoresponsive Hydrogel-Based Local Delivery of Simvastatin for the Treatment of Periodontitis.Molecular pharmaceutics · 2021Article
- GSK3 inhibitor-loaded osteotropic Pluronic hydrogel effectively mitigates periodontal tissue damage associated with experimental periodontitis.Biomaterials · 2020Article
- Rosuvastatin Prevents the Exacerbation of Atherosclerosis in Ligature-Induced Periodontal Disease Mouse Model.Scientific reports · 2020Article
- Identification of Genes Differentially Expressed in Simvastatin-Induced Alveolar Bone Formation.JBMR plus · 2019Article
- Contribution of Statins towards Periodontal Treatment: A Review.Mediators of inflammation · 2019Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
purposeSimvastatin (SIM), a HMG-CoA reductase inhibitor widely prescribed for hypercholesterolemia, has been reported to ameliorate inflammation and promote osteogenesis. Its clinical applications on these potential secondary indications, however, have been hampered by its lack of osteotropicity and poor water solubility. To address this challenge, we propose to design and evaluate the therapeutic efficacy of a novel simvastatin prodrug with better water solubility and bone affinity.
methodThe prodrug (SIM-PPi) was synthesized by directly conjugating a SIM trimer to a pyrophosphate (PPi). It was characterized and evaluated in vitro for its water solubility, osteotropicity, toxicity, anti-inflammatory and osteoinductive properties. It was then tested for anti-inflammatory and osteoinductive properties in vivo by three weekly injections into gingiva of a ligature-induced experimental periodontitis rat model.
resultsIn vitro studies showed that SIM-PPi has greatly improved water-solubility of SIM and shows strong binding to hydroxyapatite (HA). In macrophage culture, SIM-PPi inhibited LPS-induced pro-inflammatory cytokines (IL-1β, IL-6). In osteoblast culture, it was found to significantly increase alkaline phosphatase (ALP) activity with accelerated mineral deposition, confirming the osteogenic potential of SIM-PPi. When tested in vivo on an experimental periodontal bone-loss model, SIM-PPi exhibited a superior prophylactic effect compared to dose equivalent SIM in reducing inflammatory cells and in preserving alveolar bone structure, as shown in the histological and micro-CT data.
conclusionSIM-PPi may have the potential to be further developed for better clinical management of bone loss associated with periodontitis.
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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.