In present study, we formulated RT loaded PLGA-Soya lecithin-Tween 80 NPs, for the treatment of Alzheimer’s disease (AD). After formulation we optimized formulation by Response Surface Methodology (RSM) using 32 factorial design. PLGA-Soya lecithin-Tween 80 nanoparticles were synthesized by modified nanoprecipitation technique combined with self assembly. Influence of important factors on the particle size, polydispersity, entrapment efficiency and in vitro drug release were studied. FTIR and DSC studies demonstrated that there was no interaction between drug, polymers and lipid and they were compatible with each other. Prepared nanoparticle of optimized formulation (D10) showed particle size 171.74 nm, polydispersity 0.154, entrapment efficiency 66.171 % and in vitro drug release 67.336 ± 0.254% (60h). Zeta Potential and stability study for six months demonstrated that the formulations were stable at refrigerator (3-5°C) condition is most suitable for storage of nanoparticles. SEM studies results indicated that the NPs were spherical in shape and smooth at surface. In vivo behavioral studies, AchE activity analysis and histological study of hippocampus demonstrated that, the rats treated with NPs showed markedly better memory retention and better brain condition compare to pure drug treated. The study demonstrated the successful attempt to target brain with RT loaded PLGA-Soya lecithin-Tween 80 NPs, with considerable therapeutic prospective to treat AD and potential carrier for providing sustained brain delivery of RT.