Neurodegenerative diseases and brain delivery of therapeutics: Bridging the gap using dendrimers

Neurodegenerative diseases (NDs) continue to burden human lives and economic conditions. They continue to challenge the healthcare system due to the associated physiological barriers. Traditional treatment approaches are associated with symptomatic relief and are ineffective in the long run. Dendrimers stand out amongst other nanocarriers due to ease of surface modifications, internal encapsulation, and nanoscale uniformity of the molecule. Moreover, their internal core can encapsulate drug through electrostatic interactions. These are stable carriers in the nanometer size range. These either act as therapeutic agents per se or deliver the target drug across the blood-brain barrier while minimizing toxicity. Emerging as a promising non-invasive approach, they demonstrate the capability to interfere with in-vivo protein aggregation, typically associated with neurodegeneration. They assist via exerting various neuroprotective roles, such as in oxidative stress, neuroinflammation, inhibiting certain biochemical parameters, altering protein misfolding and aggregation, etc. However, certain limitations are associated with their elimination and cytotoxicity. The investigation revealed the masking of exposed cationic surfaces of dendrimers with inert substances, such as polyethylene glycol to limit their cytotoxicity. This review describes the incidences and pathophysiology of several NDs, properties, and methods of dendrimer synthesis, followed by various research to explore dendrimers potential to treat NDs.