The in vitro release of TEF and MTX from NP was 70.41 ± 1.22% and 82.43 ± 1.31% till 24 h, which showed sustained release behavior. An in vivo study showed that NPs exhibited significant decrease in ankle diameter and arthritis score and showed the least hepatotoxicity. Biochemical investigations showed insignificant changes in glutamic oxaloacetate transaminase and glutamic pyruvic transaminase levels. This evidence concerns the gene GPT and arthritic joint disease.