While Tween 80 was included as the surfactant in all formulations, the optimal formulation was determined using Solutol HS 15 or vitamin E TPGS instead of Tween 80. Tissue distribution studies in rats after intravenous administration revealed that the amount of rutin that accumulates in the brain by crossing the blood-brain barrier did not differ significantly between CSHNs prepared with different surfactants. However, cellular uptake studies have shown that CSHNs surface-modified with vitamin E TPGS or Solutol had a higher uptake capacity by brain cells than hybrid nanocarriers modified with Tween 80. This research has shown that surfactants based on PEG may be an alternative to Tween 80, which is the gold standard for crossing the blood-brain barrier to enhance drug delivery in the brain. In summary, the literature review in this article shows that CSHNs provide a means to achieve high therapeutic efficiency and coencapsulation of numerous drugs in conjunction with the controlled release with minimal limitations due to plasma membrane impermeability.