Alzheimer's disease (AD) is a neurodegenerative disease associated with progressive cognitive and memory dysfunction. Quercetin is a natural flavonoid possessing strong antioxidant and neuroprotective activities that has been identified to be of potential value in the treatment of AD by its acetylcholinesterase and butyrylcholinesterase inhibitory action. Its lack of aqueous solubility, low bioavailability, and limited passage across the blood-brain barrier (BBB) limit its clinical applications. To overcome such challenges, the present study had the objective of formulating a nano formulation targeted to the brain of quercetin with a chemically modified polyethyleneimine-based polymer. The functionalized polymer was prepared and determined by FTIR and mass spectroscopic methods that successful conjugation was achieved. Nanoparticles were formulated by solvent injection methods and compared for particle size, zeta potential, PDI, and entrapment efficiency. Optimized formulations showed particle sizes in the nano-range with monodispersity and positive surface charge. Sustained release and pH sensitivity of the drug were observed in vitro, especially under physiological pH conditions of 7.4. Pharmacokinetics demonstrated increased quercetin brain uptake using the modified formulation over plain drug. Moreover, acute toxicity experiments proved that the synthesized modified nanoparticles were safe and biocompatible, with no considerable adverse effects in treated animals. The results confirm the potential of the improved nano formulation as a promising platform for effective and targeted delivery of quercetin to the brain for the treatment of Alzheimer's disease.