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H-G-MTX is an experimental **locally injectable hierarchical drug-delivery formulation** for rheumatoid arthritis composed of degradable **hyaluronic acid microparticles** that encapsulate **peptide dendrimer-grafted methotrexate nanoparticles**. In inflamed acidic joints, the hyaluronic acid carrier is designed to release G-MTX, improving intracellular delivery of conjugated methotrexate to inflammatory cells and promoting macrophage polarization from the pro-inflammatory M1 state toward the anti-inflammatory M2 state. Preclinical data in a collagen-induced arthritis rat model suggest anti-inflammatory, cartilage-protective, and bone-preserving activity, but this appears to be a research-stage formulation rather than a marketed therapeutic product.
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