Intra-articular delivery of a methotrexate loaded nanostructured lipid carrier based smart gel for effective treatment of rheumatic diseases

Abstract

A nanostructured lipid carrier (NLC) based smart gel of methotrexate (MTX) was developed as a potential system for the treatment of rheumatic diseases (RD). NLC composed of Compritol ATO 888 as the solid lipid, Capmul MCM EP as the liquid lipid, Tween 80 as the surfactant and PEG 400 as the co-surfactant was prepared by modified hot homogenization followed by melt ultrasonication. The prepared NLC dispersion was characterized for particle size, polydispersity index (PDI), entrapment efficiency and zeta potential. The nanoparticulate dispersion was suitably gelled into the polymer matrices of Pluronic F-127 (PF-127) and Pluronic F-68 (PF-68). Two-factor three-level full factorial design was employed to determine the optimum concentrations of PF-127 and PF-68. The prepared NLC based smart gel was evaluated for viscosity, sterility, thermosensitivity, syringeability, content uniformity and in vitro release behaviour. The efficacy and biocompatibility of the NLC based smart gels were established using an adjuvant arthritis model and histology analysis, respectively. The NLCs had an average particle size of 107 ± 6 nm with a PDI of 0.365 ± 0.03, entrapment efficiency of 69.53% ± 1.23% and zeta potential of −13.54 ± 1.1 mV. The optimized NLC based smart gel (F-10) was found to be thermo-sensitive and exhibited 92.41% drug release at 108 h. The results demonstrated that MTX was evenly distributed in the optimized formulation, which was sterile and syringeable through an 18 gauze needle. A significant decrease in rat joint swelling was observed using the MTX-NLC based gel during a 28 day period. In conclusion, this MTX-NLC based gel could be a potential formulation for intra-articular treatment of inflammation in rheumatic conditions.