The aim of the present study was to develop, optimize, and evaluate methotrexate containing poloxamer 407 coated polymeric nanoparticles to enhance the concentration of drug in the brain. In the present work methotrexate loaded nanoparticles were formulated by the emulsification solvent evaporation technique. The full 32 factorial designs were employed for the determination of polymer and surfactant concentrations effects on different characters, where polymer and surfactant were two variables at three levels. The prepared nanoparticles were optimized and characterized for particle size, polydispersity, zeta potential, entrapment efficiency, scanning electron microscopy, percentage yield, in vitro drug release studies, and sterilization of polymeric nanoparticles. For the delivery of a sufficient amount of methotrexate loaded nanoparticles in the brain, these were coated by using poloxamer 407 (1-2% of total suspension volume). The particle size was observed in the Nano range and uniformity of particle size revealed by low PDI value. Thus F5 preparation showed the 192.2 nm particle sizes and its – 19.10 mv zeta potential values suggested that it created adequate repulsive forces between the nanoparticles. The percentage entrapment efficiency was observed maximum (72.4%) for the F5
preparation. The percentage yield of methotrexate loaded polymeric nanoparticles was from 58.3 to 76.7% for different preparations (F1-F9). Drug content for different polymeric nanoparticle preparations (F1-F9) was around 72%. The P-values for above-mentioned responses were found ≤ 0.05 which indicated that the model was significant. Our primary findings demonstrate that the designed methotrexate containing PLGA polymeric nanoparticles releasing the methotrexate for a longer period time. The designed preparation could be deliver sufficient amount of methotrexate in the brain. Based on findings, it is possible to exhibit coated polymeric nanoparticles as a good carrier for the increased delivery of methotrexate