The blood-brain barrier is the most important barrier preventing the passage of neurotherapeutic agents from the bloodstream to the brain. Among the strategies developed to overcome this barrier, nanosized drug delivery systems coated with surfactants were one of the approaches that yielded the greatest success. To determine the efficacy of CSHNs systems under this approach, Ishak et al. developed CSHNs systems whose surface was modified with PEG-based surfactants such as vitamin TPGS or Solutol HS 15 and compared them for the first time in the literature with the surfactant Tween 80, which is the most promising material to cross the blood-brain barrier . In this study, CSHNs were prepared by a modified nanoprecipitation technique, and the flavonoid rutin extracted from the flowers of Calendula officinalis L., which is considered a promising agent for the treatment of Alzheimer's disease, was encapsulated into the core structure of CSHNs. PLGA was used as the primary core material, while lecithin and soybean phosphatidylcholine were used as lipid coating materials.