Mannose-mediated nanodelivery of methotrexate to macrophages augments rheumatoid arthritis therapy.
Biomater Sci
; 11(6): 2211-2220, 2023 Mar 14.
Article
en En
| MEDLINE
| ID: mdl-36748266
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 (â¼18 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-1ß compared with free MTX and PMTX. In vivo 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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Artritis Reumatoide
/
Metotrexato
Aspecto:
Patient_preference
Límite:
Humans
Idioma:
En
Revista:
Biomater Sci
Año:
2023
Tipo del documento:
Article