Regional brain distribution of PLGA nanoparticles functionalized with glutathione or phenylalanine dipeptide

Neurodegenerative diseases are chronic disorders affecting millions of people with their prevalence constantly increasing worldwide. The blood-brain barrier plays a key role in the design of successful treatments for these pathologies. Nanotechnology has the potential to improve treatment of CNS disorders and facilitate effective drug transfer. For this, biodegradable poly (lactic-co-glycolic acid) nanoparticles (PLGA NPs) are promising strategies as they can be surface-tailored with functionalized molecules for site-specific brain targeting. In our work PLGA NPs loaded with a fluorescent marker (rhodamine B) and functionalized with glutathione or phenylalanine dipeptide have been developed, characterized and analyzed for their passage across the BBB and distribution 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 amino acid transporter 1 (LAT-1) may be involved. One hour after their administration both functionalized formulations predominantly reached the hippocampus followed by the cortex and substantia nigra. Average values of intensity of 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 the potential importance of the results obtained as the presence of the NPs in the brain 2 h after their administration counteracts the efflux activity of the P-glycoprotein. In addition, none of the nanosystems caused tissue damage in the hippocampus, cortex or substantia nigra.