Neurodegenerative diseases impact millions of people globally and are emerging as an imminent challenge due to the rapid aging of the population. The current treatments only focus on relieving their symptoms, so it is necessary to adopt innovative strategies. However, delivering pharmacological agents directly into the brain is difficult because of the presence of the Blood–Brain Barrier (BBB). To overcome this obstacle, nanotransporters such as phytosomes have been developed. This study reports the preparation and characterization of phosphatidylcholine (PC) phytosomes based on hydroethanolic extracts of three macroalgae: Ascophyllum nodosum (L.) Le Jolis (AN), Bifurcaria bifurcata R.Ross (BB), and Fucus spiralis L. (FS). Additionally, some phytosomes were functionalized with polyethylene glycol (PEG) and apolipoprotein E (ApoE). Phytosome characterization was carried out in terms of encapsulation rate, size, polydispersity index (PDI), zeta potential, and stability, and the efficacy of passage through the BBB was tested using an in vitro transwell model based on hCMEC/D3 cells. The results showed a high percentage of extract bound to PC (from 74.9 to 80.3 %), and tests conducted over three weeks showed the stability of the phytosomes developed. There was a notable distinction between the functionalized and non-functionalized phytosomes, reflected in the values of their sizes (from 117.71 to 167.73 nm for non-functionalized and from 277.07 to 361.44 nm for PEG-ApoE phytosomes), PDIs (0.286-0.411 for non-functionalized and 0.389-0.539 for functionalized phytosomes), and zeta potentials (1.91-2.22 and -3.31- -0.68 mV for non-functionalized and functionalized phytosomes), respectively. Regarding their ability to cross the BBB, the functionalization of phytosomes with ApoE did not prove to be a crucial step, perhaps due to the low amount of ApoE used (1%), as all of the nanotransporters always passed through the hCMEC/D3 cell monolayer, regardless of their formulation.