Quality by design driven development and optimization of teriflunomide loaded nanoliposomes for treatment of rheumatoid arthritis: An in vitro and in vivo assessments

The objective of the present research was to develop teriflunomide-loaded nanoliposomes by thin-film hydration technique for the management of rheumatoid arthritis. Quality by design approach was applied statistically for the optimization of the teriflunomide-nanoliposomalformulation. The vesicle size, polydispersity index, zeta potential and entrapment efficiency of the optimized teriflunomide-nanoliposomal formulation was found to be 128.92 ± 5.42 nm, 0.206 ± 0.06, +12.6 ± 1.2 mV and 73.94 ± 4.32%, respectively. The optimized formulation exhibited initial burst release followed by sustained release for 24 h. Hemolytic toxicity assay and syringe ability test results revealed that the nanoliposomal formulation was safe and effective after intravenous administration. Rhodamine B loaded nanoliposomal formulation showed significantly higher cellular uptake compared with free Rhodamine B solution in RAW 264.7 cells. In vivo pharmacokinetic study results revealed that the optimized teriflunomide-nanoliposomal formulation followed sustained release and showed higher therapeutic efficacy of the drug at the inflammatory site compared with teriflunomide-solution. Therefore, it can be concluded that the developed teriflunomide-nanoliposomal formulation could improve therapeutic efficacy in the management of rheumatoid arthritis after intravenous administration.