Designing nanocarriers to overcome the limitations in conventional drug administration for Parkinson’s disease

Abstract

Neurodegenerative diseases (NDs) have become one of the leading causes of death and disability worldwide, and cause enormous pain and suffering for both patients and their families. Some of the most common NDs include Alzheimer’s disease, Parkinson’s disease (PD) and Huntington’s disease, among others (Feng, 2020). PD is a widespread neurodegenerative disease that affects more than 10 million people worldwide (No author listed, 2021). The direct cause of the disease is unknown, but it is characterized by the selective degeneration of dopaminergic neurons in the midbrain in the substantia nigra. This leads to the depletion of dopamine (3,4-dihydroxyphenethylamine, DA) in the striatum of patients, in addition to the existence of abnormal α-synuclein in nerve cells and the development of toxic protein aggregates in neurons called Lewy bodies, which causes muscle stiffness, slowness of movements and tremors. It is believed that a combination of genetic and environmental factors may be the cause of PD, but the exact reason for the disease is not yet fully understood. In the treatment of neurological diseases, particularly in PD, NPs can play a remarkable role mainly due to their distinctive thermal, magnetic, and physicochemical properties, such as shape, small size, large specific surface area, hydrophobicity, high loading capacity of different moieties and drugs, chemistry and surface charge, and coating and easy functionalization. The latter allows modifying the NPs surface area with various functional molecules, and therefore introducing the capability that NPs reach target sites by means of active targeting strategies for enhanced uptake in specific cells. Therefore, NPs can help DA or alternative therapies to ensure that they: are not metabolized with uncontrolled effects, do not interfere with other organ function, have lasting effects as a consequence of the slow release in a continuous and sustained way, and are even able to cross the BBB to reach the target sites and escape the reticuloendothelial system, thus reducing drug administration and, therefore, reducing side effects (both adverse and otherwise).