Title : Methotrexate nanoparticles ameliorate Freund’s complete adjuvant induced arthritis in Wistar rats
Abstract:
Rheumatoid arthritis (RA) is a chronic autoimmune disease and is characterized by inflammation, tissue damage and functional impairment. Methotrexate (MTX) is used in treatment of RA but numerous adverse effects are associated with its use. It has fast clearance as well. These factors lead to poor patient compliance. In order to reduce these problems, the current study was conducted which is focused on engineering of MTX loaded biodegradable nanoparticles and to explore their effect in Freund’s complete adjuvant (FCA) induced Wistar rats. Experimental animals (n=30) were randomly divided into 5 groups where 1st group was healthy control, 2nd was arthritic control, 3rd was MTX administered while 4th and 5th were treated with methotrexate nanoparticles (MTX-NPs) at different dose levels. Nanoparticles were prepared using biodegradable polymer, chitosan, by method of solvent evaporation, and were characterized by zeta size, fourier transform infrared spectroscopy and polydispersity index. The prepared NPs exhibited size of 190nm and PDI of 0.25. After FCA administration, rise in paw thickness was recorded up to 21 days which was ameliorated by MTX-NPs (high dose). The pro-inflammatory markers level i.e. IL-6 and TNF-α as well as superoxide dismutase & catalase were also found to be reduced in MTX-NPs treated groups in comparison to arthritic group. The ameliorated effect of MTX-NPs was also confirmed by hematological, biochemical, radiological and histopathological investigations of experimental rats. Based upon these findings, it is concluded that MTX-NPs might be promising candidates for treatment of FCA induced arthritic rats. However, further studies are required for safety of MTX-NPs as well as for dose optimization of these nanoparticles.
