Applications of Exosomes in Targeted Drug Delivery for the Treatment of Parkinson's Disease: A Review of Recent Advances and Clinical Challenges

Parkinson's disease (PD) is one of the most prevalent and severe neurodegenerative disease affecting more than 6.1 million people globally. It is characterized by age-related progressive deterioration of neurological functions caused by neuronal damage or neuronal death. During PD, the dopamineproducing cells in the substantia nigra region of the brain degenerate, which leads to symptoms like resting tremors and rigidity. Treatment of PD is very challenging due to the blood-brain barrier, which restricts the drug from reaching the brain. Conventional drug delivery systems possess a limited capacity to cross the blood barrier, leading to low bioavailability and high toxicity (due to off-site drug release). Therefore, it becomes necessary to accelerate the development of novel drug delivery systems, including nanoparticles, microemulsions, matrix systems, solid dispersions, liposomes, and solid lipid nanopartides for the treatment of PD. Exosomes are biological lipid bilayer membrane vesicles produced by nearly all mammalian cells. The characteristics of vesicles are unique to their cell of origin and are primarily involved in intracellular communication. Exosomes, due to their nanoscale size, could easily permeate across the central nervous system, which makes them ideal for targeting the neurons in the substantia nigra. Exosomes could be efficient drug carrier systems for brain targeting, which can increase the efficacy of the drug and minimize the side effects. The review aims at providing a broad updated view of exosomes and their application in the treatment of PD.