The promising potential of nano-structured lipid carrier (NLC) polymeric gel of CUR as an effective treatment for rheumatoid arthritis by intra-articular route of administration was investigated. NLC composed of cetylpalmitate, Labrafac PG & Captex 200, Tween 80 and Labrasol. The hot homogenization method employed by melt ultrasonication was used. The formulated NLC dispersions were characterized and were suitably dispersed into the matrix of pluronic F-127(PLF-127) and pluronic F-68 (PLF-68). A two-factor three-level full factorial design was employed to deduce the optimal concentrations of PLF-127 and PLF-68. The optimized formulations were sterilized by gamma radiation. The formulated NLC smart gels were characterized and evaluated for various parameters. The efficacy evaluation by antigen-induced monoarthritis model and biocompatibility testing by histopathological studies was performed. Formulated NLCs exhibited an average particle size of 165.12 nm, entrapment efficiency of 72.15%, and zeta potential of -21.67 mV. The optimized CUR-NLC smart gel was demonstrated to have a sol-gel transformation at 33.21 °C and 94.32% drug release at 84 h. NLC's which were sterile and easily syringeable, continued to remain within the colloidal range. CUR-NLC smart gels were found to be biocompatible and showed a significant reduction in rat knee joint inflammation compared to free drug.
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