ArticleJournal of controlled release : official journal of the Controlled Release Society2015
Simvastatin prodrug micelles target fracture and improve healing.
Article in Journal of controlled release : official journal of the Controlled Release Society, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 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
18 citing papers in PubMed, 35 citations in OpenAlex.
- Effect of Alginate Coatings on Hydroxyapatite/β-Tricalcium Phosphate Scaffold Behavior.Journal of functional biomaterials · 2026Article
- Review
- Bone Targeting Nanoparticles for the Treatment of Osteoporosis.International journal of nanomedicine · 2024Review
- An update on the advances in the field of nanostructured drug delivery systems for a variety of orthopedic applications.Drug delivery · 2023Article
- Chitosan Nanoparticle/Simvastatin for Experimental Maxillary Bony Defect Healing: A Histological and Histomorphometrical Study.Biomimetics (Basel, Switzerland) · 2023Article
- Bone-Targeting Systems to Systemically Deliver Therapeutics to Bone Fractures for Accelerated Healing.Current osteoporosis reports · 2020Review
- Adjuvant Drug-Assisted Bone Healing: Advances and Challenges in Drug Delivery Approaches.Pharmaceutics · 2020Review
- Autophagy Modulators: Mechanistic Aspects and Drug Delivery Systems.Biomolecules · 2019Review
- Development of controlled drug delivery systems for bone fracture-targeted therapeutic delivery: A review.European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V · 2018Review
- Knockdown of Ggps1 in chondrocyte expedites fracture healing by accelerating the progression of endochondral ossification in mice.Journal of bone and mineral metabolism · 2018Article
- Time-series expression profile analysis of fracture healing in young and old mice.Molecular medicine reports · 2017Article
- Fracture-Targeted Delivery of β-Catenin Agonists via Peptide-Functionalized Nanoparticles Augments Fracture Healing.ACS nano · 2017Article
- Pharmacokinetic and Biodistribution Studies of HPMA Copolymer Conjugates in an Aseptic Implant Loosening Mouse Model.Molecular pharmaceutics · 2017Article
- Advances in Controlled Drug Delivery for Treatment of Osteoporosis.Current osteoporosis reports · 2016Review
- The Evaluation of Therapeutic Efficacy and Safety Profile of Simvastatin Prodrug Micelles in a Closed Fracture Mouse Model.Pharmaceutical research · 2016Article
- Biodistribution of Fracture-Targeted GSK3β Inhibitor-Loaded Micelles for Improved Fracture Healing.Biomacromolecules · 2015Article
- The Effect of Local Simvastatin on Alveolar Bone Regeneration, Pain, and Swelling After Tooth Extraction: a Systematic Review.Journal of oral & maxillofacial researchReview
- STATINS AND BONE HEALTH: A MINI REVIEW.Actualizaciones en osteologiaArticle
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
Simvastatin (SIM), a widely used anti-lipidemic drug, has been identified as a bone anabolic agent. Its poor water solubility and the lack of distribution to the skeleton, however, have limited its application in the treatment of bone metabolic diseases. In this study, an amphiphilic macromolecular prodrug of SIM was designed and synthesized to overcome these limitations. The polyethylene glycol (PEG)-based prodrug can spontaneously self-assemble to form micelles. The use of SIM trimer as the prodrug's hydrophobic segment allows easy encapsulation of additional free SIM. The in vitro studies showed that SIM/SIM-mPEG micelles were internalized by MC3T3 cells via lysosomal trafficking and consistently induced expression of both BMP2 and DKK1 mRNA, suggesting that the prodrug micelle retains the biological functions of SIM. After systemic administration, optical imaging suggests that the micelles would passively target to bone fracture sites associated with hematoma and inflammation. Furthermore, flow cytometry study revealed that SIM/SIM-mPEG micelles had preferred cellular uptake by inflammatory and resident cells within the fracture callus tissue. The treatment study using a mouse osteotomy model validated the micelles' therapeutic efficacy in promoting bone fracture healing as demonstrated by micro-CT and histological analyses. Collectively, these data suggest that the macromolecular prodrug-based micelle formulation of SIM may have great potential for clinical management of impaired fracture healing.
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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.