Polyethyleneimine (PEI), a cationic polymer, has been extensively studied by researchers for its applications in gene delivery and drug transport. However, due to its toxicity, there are some limitations, such as cytotoxicity and non-biodegradability. In this study, PEI was conjugated with polyethylene glycol (PEG) to enhance its stability and prolong its residence time in the body. To make it more suitable for brain delivery, we further modified it with the addition of an amino acid, phenylalanine, which improves its physicochemical properties for brain delivery in Alzheimer's disease (AD) and other neurodegenerative disorders. Quercetin is a flavonoid with notable pharmacological effects and promising therapeutic potential in AD. This novel polymer is utilized to prepare nanoparticles (NPs) for the effective delivery of quercetin in the brain. The synthesis of acryl PEI derivatives is the first step, followed by PEGylation of the acryl PEI derivative, and further derivatization of PEI-PEG with a disulfide linker. Lastly, the above compound is attached to the amino acid phenylalanine, as confirmed by FT-IR, mass spectroscopy, and DSC. Then, after preparation of nanoparticles, which were evaluated through particle size, zeta potential, PDI, SEM, and in vitro release, the MTT assay was performed to ensure that cell viability remained above 80%, and the ex vivo intestinal permeability of the novel polymer NPs remained at 5μg/cm. A further blood–brain barrier permeation study was carried out, in which the novel polymer showed the highest permeability. The histopathological evaluation of the brain hippocampus region, Ca1, was tested for novel polymer and formulation, and the absence of observable variations such as lesions, necrosis, and inflammation,confirmed that the synthesized polymer was non-toxic and had high permeability. Studies further demonstrated that the polymer and its NPs are safe and capable of effectively crossing the blood–brain barrier, highlighting their potential for targeted neurological therapies.