RT Journal Article T1 Regional brain distribution of PLGA nanoparticles functionalized with glutathione or phenylalanine dipeptide A1 Negro Álvarez, María Sofía Elisa A1 Barcia Hernández, Emilia María A1 Fernández Carballido, Ana María A1 Alonso, Mario A1 Paccione, Nicola A1 Rahmani, Mahdieh A1 Montejo, Consuelo A1 García-García, Luis AB Neurodegenerative diseases are chronic disorders affecting millions of people with their prevalence constantlyincreasing worldwide. The blood-brain barrier plays a key role in the design of successful treatments for thesepathologies. Nanotechnology has the potential to improve treatment of CNS disorders and facilitate effectivedrug transfer. For this, biodegradable poly (lactic-co-glycolic acid) nanoparticles (PLGA NPs) are promisingstrategies as they can be surface-tailored with functionalized molecules for site-specific brain targeting. In ourwork PLGA NPs loaded with a fluorescent marker (rhodamine B) and functionalized with glutathione orphenylalanine dipeptide have been developed, characterized and analyzed for their passage across the BBB anddistribution in different brain areas of Wistar rats.Surface functionalization of the NPs with glutathione or phenylalanine (formulations NP-GSH-Rh and NP-PHE2-Rh) favoured their passage across the BBB process in which glutathione transporter and L-type aminoacid transporter 1 (LAT-1) may be involved. One hour after their administration both functionalized formulationspredominantly reached the hippocampus followed by the cortex and substantia nigra. Average values of intensityof fluorescence reached in the hippocampus showed statistically significant differences when compared to non-functionalized NPs and remained higher in this area 2 h after administration which allows us to highlight thepotential importance of the results obtained as the presence of the NPs in the brain 2 h after their administrationcounteracts the efflux activity of the P-glycoprotein. In addition, none of the nanosystems caused tissue damagein the hippocampus, cortex or substantia nigra. PB Elsevier SN 1773-2247 YR 2025 FD 2025 LK https://hdl.handle.net/20.500.14352/118819 UL https://hdl.handle.net/20.500.14352/118819 LA eng NO Alonso M, Barcia E, Negro S, Paccione N, Rahmani M, Montejo C, García-García L, Fernández-Carballido A. Regional brain distribution of PLGA nanoparticles functionalized with glutathione or phenylalanine dipeptide. Journal of Drug Delivery Science and Technology 2025;105:106680. https://doi.org/10.1016/j.jddst.2025.106680. NO Universidad Complutense de Madrid. Grupo de investigación 910939 DS Docta Complutense RD 6 abr 2025