Development of Methotrexate Complexes Endowed with New Biological Properties Envisioned for Musculoskeletal Regeneration in Rheumatoid Arthritis Environments.
Daniel Fernández-VillaRosa Ana Ramírez-JiménezInmaculada AranazNiuris AcostaBlanca Vázquez-LasaLuis RojoPublished in: International journal of molecular sciences (2022)
Methotrexate (MTX) administration is the gold standard treatment for rheumatoid arthritis (RA), but its effects are limited to preventing the progression of the disease. Therefore, effective regenerative therapies for damaged tissues are still to be developed. In this regard, MTX complexes of general molecular formula M(MTX)·xH 2 O, where M = Sr, Zn, or Mg, were synthesized and physicochemically characterized by TGA, XRD, NMR, ATR-FTIR, and EDAX spectroscopies. Characterization results demonstrated the coordination between the different cations and MTX via two monodentate bonds with the carboxylate groups of MTX. Cation complexation provided MTX with new bioactive properties such as increasing the deposition of glycosaminoglycans (GAGs) and alternative anti-inflammatory capacities, without compromising the immunosuppressant properties of MTX on macrophages. Lastly, these new complexes were loaded into spray-dried chitosan microparticles as a proof of concept that they can be encapsulated and further delivered in situ in RA-affected joints, envisioning them as a suitable alternative to oral MTX therapy.
Keyphrases
- rheumatoid arthritis
- stem cells
- disease activity
- drug delivery
- anti inflammatory
- ankylosing spondylitis
- magnetic resonance
- high dose
- gene expression
- interstitial lung disease
- mesenchymal stem cells
- systemic lupus erythematosus
- high resolution
- bone marrow
- human milk
- risk assessment
- oxidative stress
- dna damage response
- idiopathic pulmonary fibrosis