Formulation development and evaluation of smart gels for anti arthritic drugs

Abstract

NLC based smart gels of MTXandCUR were developed separately as potential systems for the treatment of RA. NLC composed of solid lipid, liquid lipid,surfactantandco-surfactant were prepared by modified hot homogenization followed by melt ultrasonication. A three-factor, three-level Box Behnken experimental design was used to optimize the NLC. The prepared NLC dispersions were characterized forparticle size, scanning electron microscopy, entrapment efficiency, zeta potentialanddrug loading. The nanoparticulate dispersions were suitably gelled into the polymermatrices of Pluronic F-127 (PF-127)andPluronic F-68 (PF-68). Two-factor three-levelfull factorial design was employed to determine the optimum concentrations of PF-127and PF-68. The optimized formulations were sterilized by gamma irradiation. The prepared NLC based smart gels were evaluated for thermosensitivity, syringeability, invitro release, viscosity, drug contentandsterility. The efficacyandbiocompatibility ofthe NLC based smart gels of both drugs were established using an antigen inducedmonoarthritis modelandhistological analysis, respectively.The optimized compositions of MTXandCUR loaded NLC revealed sphericalshape particles with an average particle size of 107.4 nmand165.12 nm respectively.The MTX-NLC showed entrapment efficiency of 79.53%, zeta potential of -13.54 mVand drug loading of 9 %. The CUR-NLC showed entrapment efficiency of 72.15%, zetapotential of -21.67 mVanddrug loading of 10.85%. The optimized NLC based smartgels of both drugs were found to be thermo-sensitive; displayed sol to gel transitionvalue lower than the body temperatureandshowed faster onset yet optimum prolonglocalized drug release. The MTX-NLC based smart gel showed 92.41% drug release at 108 h while CUR-NLC based smart gel showed 94.32% drug release at 84 h. The NLCs remained within the colloidal rangeandwere uniformly dispersed after being suitably gelled by PF-127andPF-68; which were sterileandsyringe able through an18 gauze needle. A significant decrease in the rat knee joint swelling was observed.