Designing an effective intranasal (IN) delivery mechanism for the water soluble anti-epileptic drug levetiracetam (LEV) for brain targeting effect was the main objective of this work. By using the nanoprecipitation process and the polymer Eudragit S100, nanospheres were prepared. Different weights of Eudragit S100 and varied concentration of poloxamer 188 (stabilizer) were employed. The produced levetiracetam nanospheres exhibited sufficient entrapment efficiency range from 79.2% to 93.5%, with zeta potential values from 26.7mV to 40.6 mV. The developed Nanospheres had spherical shape and nanosize range (10.44 to 79.07 nm). In situ gels prepared from Poloxamer 407 (18%) and different mucoadhesive polymers (Na CMC and chitosan) were evaluated for gelling time, gelling temperature, pH and rheology. The nanosphere in situ gels were further evaluated for in vitro drug release revealed 73.6% to 84.5% release within 8 hrs. The optimum in situ gel formula was evaluated for stability, and evaluated for ex-vivo permeation through nasal mucosa.