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Mannose-mediated nanodelivery of methotrexate to macrophages augments rheumatoid arthritis therapy. | LitMetric

Mannose-mediated nanodelivery of methotrexate to macrophages augments rheumatoid arthritis therapy.

Biomater Sci

Biomedical Polymers Laboratory, College of Chemistry, Chemical Engineering and Materials Science, and State Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou, 215123, P. R. China.

Published: March 2023

AI Article Synopsis

  • * Researchers developed mannose-installed chimaeric polymersomes (Man-PMTX) for targeted delivery of MTX, which showed improved drug loading, minimized side effects, and better uptake by activated macrophages compared to traditional treatments.
  • * Man-PMTX effectively reduces inflammation and promotes anti-inflammatory responses in macrophages, leading to better outcomes in treating RA by protecting joints and reducing damage from the disease.

Article Abstract

Rheumatoid arthritis (RA) is a chronic autoimmune disease that gravely jeopardizes the quality of life of numerous people. Methotrexate (MTX) is a disease-modifying anti-rheumatic drug commonly used in clinics; however, it suffers from slow onset, moderate efficacy, and adverse reactions such as renal dysfunction, myelosuppression, and bone erosion after long-term treatment. Here, we explored macrophage targeted delivery of MTX using mannose-installed chimaeric polymersomes (Man-PMTX) as an advanced treatment for RA. Man-PMTX exhibited high (∼18 wt%) and robust loading of MTX, uniform size of 51-55 nm, minimal hemolytic activity, and glutathione-actuated drug release property. Man-PMTX showed better uptake by activated macrophages than PMTX, and more repolarization of bone marrow-derived macrophages (BMDMs) to anti-inflammatory M2 type macrophages and less secretion of TNF-α and IL-1β compared with free MTX and PMTX. studies revealed that Man-PMTX showed significantly higher accumulation in inflammatory joints than in healthy joints and effectively treated RA by relieving inflammation, repolarizing macrophages from M1 type to M2 type, and mitigating proinflammatory cytokines. Accordingly, Man-PMTX effectively protected the synovium and bone from damage. Mannose-mediated nanodelivery of methotrexate to macrophages appears to be an attractive strategy to augment rheumatoid arthritis therapy.

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Source
http://dx.doi.org/10.1039/d2bm02072fDOI Listing

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