Barcia, EmiliaGonzález, Juan FranciscoGarcía García, LuisVilla Hermosilla, Mónica CarolinaNegro, SofíaFraguas Sánchez, Ana IsabelFernández Carballido, AnaAlonso González, MarioMontejo Rubio, María ConsueloUniversidad San Pablo-CEU. Facultad de Farmacia2024-01-102024-01-102022-10-31Alonso, M.; Barcia, E.; González, J.-F.; Montejo, C.; García-García, L.; Villa-Hermosilla, M.-C.; Negro, S.; Fraguas-Sánchez, A.-I.; Fernández-Carballido, A. Functionalization of Morin-Loaded PLGA Nanoparticles with Phenylalanine Dipeptide Targeting the Brain. Pharmaceutics 2022, 14, 2348. https://doi.org/10.3390/ pharmaceutics141123481999-4923http://hdl.handle.net/10637/14775Alzheimer’s disease (AD) is the most prevalent neurodegenerative disorder, with its incidence constantly increasing. To date, there is no cure for the disease, with a need for new and effective treatments. Morin hydrate (MH) is a naturally occurring flavonoid of the Moraceae family with antioxidant and anti-inflammatory properties; however, the blood–brain barrier (BBB) prevents this flavonoid from reaching the CNS when aiming to potentially treat AD. Seeking to use the LAT-1 transporter present in the BBB, a nanoparticle (NPs) formulation loaded with MH and functionalized with phenylalanine-phenylalanine dipeptide was developed (NPphe-MH) and compared to non-functionalized NPs (NP-MH). In addition, two formulations were prepared using rhodamine B (Rh-B) as a fluorescent dye (NPphe-Rh and NP-Rh) to study their biodistribution and ability to cross the BBB. Functionalization of PLGA NPs resulted in high encapsulation efficiencies for both MH and Rh-B. Studies conducted in Wistar rats showed that the presence of phenylalanine dipeptide in the NPs modified their biodistribution profiles, making them more attractive for both liver and lungs, whereas non-functionalized NPs were predominantly distributed to the spleen. Formulation NPphe-Rh remained in the brain for at least 2 h after administration.enopen accessAlzheimer’s diseaseMorin hydratePLGANanoparticlesBlood–brain barrierRhodamine BArtículo10.3390/ pharmaceutics14112348https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es