Formulation and evaluation of osteotropic drug delivery system of methotrexate with a potential for passive bone targeting

In the present research, methotrexate (MTX) loaded ultra-small PLGA nanoparticles were formulated with an aim of passively targeting the bone for effective treatment of metastatic condition. Formulations were prepared by using 3 2 factorial designs to evaluate the impact of the formulation variables on the dependant variables. The prepared formulations were subjected for nano-characterization and in vitro haemolysis evaluation. Nano-characterization with Malvern particle size analyser depicted a particle size below 10 nm, zeta potential (>30) indicating a very high stability with entrapment efficiency of formulation (>60 %) and drug release of >80 % sustaining for 7 days. Kinetic modelling showed that the formulations showed best fit for Korsmeyer Peppas model with r value of 0.9875. TEM and AFM studies showed ultra small nanoparticles with a spherical shape and smooth surface respectively. In-vitro bone affinity studies showed that the nanoformulation had higher affinity for Hydroxyapatite than the pure drug alone. In-vitro haemolytic assay showed a reduced haemotoxicity of the MTX when encapsulated in a nanosystem rather the pure drug.