Surface Functionalization of PLGA Nanoparticles to Increase Transport across the BBB for Alzheimer’s Disease

Alzheimer’s disease (AD) is a chronic neurodegenerative disorder that accounts for about 60% of all diagnosed cases of dementia worldwide. Although there are currently several drugs marketed for its treatment, none are capable of slowing down or stopping the progression of AD. The role of the blood-brain barrier (BBB) plays a key role in the design of a successful treatment for this neurodegenerative disease. Nanosized particles have been proposed as suitable drug delivery systems to overcome BBB with the purpose of increasing bioavailability of drugs in the brain. Biodegradable poly (lactic-co-glycolic acid) nanoparticles (PLGA-NPs) have been particularly regarded as promising drug delivery systems as they can be surface-tailored with functionalized molecules for site-specific targeting. In this review, a thorough discussion about the most recent functionalization strategies based on PLGA-NPs for AD and their mechanisms of action is provided, together with a description of AD pathogenesis and the role of the BBB in brain targeting.