Injectable Click-Crosslinked Hyaluronic Acid Depot To Prolong Therapeutic Activity in Articular Joints Affected by Rheumatoid Arthritis
| Autor: | Seung Hun Park, Min Ju Kim, Byoung-Hyun Min, Hyeon Jin Ju, Ji Young Seo, Moon Suk Kim, Xiang Yun Yin |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
musculoskeletal diseases
Male Biodistribution Materials science Depot 02 engineering and technology Pharmacology 010402 general chemistry 01 natural sciences Injections Intra-Articular Glycosaminoglycan Arthritis Rheumatoid chemistry.chemical_compound Mice Chondrocytes In vivo Hyaluronic acid medicine Distribution (pharmacology) Animals Humans General Materials Science Tissue Distribution skin and connective tissue diseases Glycosaminoglycans Interleukin-6 Tumor Necrosis Factor-alpha Hydrogels 021001 nanoscience & nanotechnology medicine.disease 0104 chemical sciences Rats Methotrexate RAW 264.7 Cells chemistry Rheumatoid arthritis Delayed-Action Preparations Joints 0210 nano-technology medicine.drug |
| Zdroj: | ACS applied materialsinterfaces. 11(28) |
| ISSN: | 1944-8252 |
| Popis: | The aim of this study was to design a click-crosslinked hyaluronic acid (HA) (Cx-HA) depot via a click crosslinking reaction between tetrazine-modified HA and trans-cyclooctene-modified HA for direct intra-articular injection into joints affected by rheumatoid arthritis (RA). The Cx-HA depot had significantly more hydrogel-like features and a longer in vivo residence time than the HA depot. Methotrexate (MTX)-loaded Cx-HA (MTX-Cx-HA)-easily prepared as an injectable formulation-quickly formed an MTX-Cx-HA depot that persisted at the injection site for an extended period. In vivo MTX biodistribution in MTX-Cx-HA depots showed that a high concentration of MTX persisted at the intra-articular injection site for an extended period, with little distribution of MTX to normal tissues. In contrast, direct intra-articular injection of MTX alone or MTX-HA resulted in rapid clearance from the injection site. After intra-articular injection of MTX-Cx-HA into rats with RA, we noted the most significant RA reversal, measured by an articular index score, increased cartilage thickness, extensive generation of chondrocytes and glycosaminoglycan deposits, extensive new bone formation in the RA region, and suppression of tumor necrosis factor-α or interleukin-6 expression. Therefore, MTX-Cx-HA injected intra-articularly persists at the joint site in therapeutic MTX concentrations for an extended period, thus increasing the duration of RA treatment, resulting in an improved relief of RA. |
| Databáze: | OpenAIRE |
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