ArticleJournal of controlled release : official journal of the Controlled Release Society2019
Glatiramer acetate persists at the injection site and draining lymph nodes via electrostatically-induced aggregation.
Article in Journal of controlled release : official journal of the Controlled Release Society, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 36 citations in OpenAlex.
- Therapeutic Immunomodulation of Tumor-Lymphatic Crosstalk via Intratumoral Immunotherapy.Molecular pharmaceutics · 2024Review
- Glatiramer acetate in situ forming gel, a new approach for multiple sclerosis treatment.Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences · 2024Article
- Feeding Next-Generation Nanomedicines to Europe: Regulatory and Quality Challenges.Advanced healthcare materials · 2023Article
- The Role of the Intestinal Microbiome in Multiple Sclerosis-Lessons to Be Learned from Hippocrates.Biology · 2023Review
- A window of opportunity trial evaluating intratumoral injection of Copaxone® in patients with percutaneously accessible tumors.Translational medicine communications · 2023Article
- Development of an In Vitro System To Emulate an In Vivo Subcutaneous Environment: Small Molecule Drug Assessment.Molecular pharmaceutics · 2022Article
- Changing the daily injection of glatiramer acetate to a monthly long acting product through designing polyester-based polymeric microspheres.BioImpacts : BI · 2022Article
- Tetrameric Fluorescent Antigen Arrays for Single-Step Identification of Antigen-Specific B Cells.Journal of visualized experiments : JoVE · 2020Article
- Synthetic Cationic Autoantigen Mimics Glatiramer Acetate Persistence at the Site of Injection and Is Efficacious Against Experimental Autoimmune Encephalomyelitis.Frontiers in immunology · 2020Article
- Linking autoantigen properties to mechanisms of immunity.Advanced drug delivery reviews · 2020Review
Corrections and comments
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
Glatiramer acetate (GA) is widely prescribed for the treatment of relapsing-remitting multiple sclerosis, however, the mechanism of action is still not fully understood. We investigated the structural properties of GA and examined alterations to the drug upon injection into the subcutaneous space. First, a variety of biophysical characterization techniques were employed to characterize GA in solution. GA was found to exist as alpha helices in solution with a hydrodynamic radius of ~3 nm in size. To simulate GA behavior at the site of injection, GA was injected into a solution of 1.5 MDa hyaluronic acid (HA). Visible aggregates were observed immediately upon injection and subsequent testing indicated aggregation was driven by electrostatic interactions between the positively-charged GA and negatively-charged HA. In vivo testing confirmed GA formed spherical particles in the nano- to micrometer size range, suggesting this mechanism contributes to persistence at the injection site and in draining lymph nodes. The aggregates were found to associate with glycosaminoglycans, suggesting an electrostatic mechanism of induced aggregation like the simulated injection. These novel observations may help explain the complex immunomodulatory mechanisms of GA and adverse injection site reactions seen in patients.
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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.