Background:
Parkinson’s disease (PD) is one of the most common neurological disorders that can severely affect
the ability to perform daily activities. The clinical presentation of PD includes motor and nonmotor symptoms. The motor
symptoms generally involve movement conditions like tremors, rigidity, slowness, and impaired balance. In contrast, the
nonmotor symptoms are often not apparent but can affect various organ systems, such as the urinary and gastrointestinal
systems, and mental health. Gene mutations and toxic environmental factors have contributed significantly to PD;
nevertheless, its cause and underlying mechanism remain unknown. Currently, treatments such as dopamine agonists, RNA
molecules, and antioxidants can, to some extent, alleviate the motor symptoms triggered by PD. However, these medicines
cannot effectively halt ongoing dopaminergic damage, mainly because the blood-brain barrier (BBB) lowers the efficiency
of drug delivery. Recently, extracellular vesicles (EVs), a novel drug delivery platform, have been widely used in various
neurological diseases, including stroke and brain tumors, because of their excellent biocompatibility, their ability to
penetrate the BBB without toxicity, and their target specificity. EVs thus provide a promising therapeutic for treating PD.
Objective:
This review focuses on novel therapies based on EVs in practice. Herein, we briefly introduce the biogenesis,
composition, isolation, and characterization of EVs, and we discuss strategies for loading therapeutic agents onto EVs and
recent applications for PD treatment. Moreover, we discuss perspectives on the direction of preclinical and clinical studies
regarding novel and effective therapies.
Methods:
A literature search regarding PD treatment based on extracellular vesicles was performed in PubMed (updated in
June 2020). Treatment, therapy, drug delivery, extracellular vesicles, and their combinations were the search queries. Both
systematic reviews and original publications were included. Searched results were selected and compared based on
relevance. Articles published in the last five years were given top priority.
Conclusion:
PD is a heterogeneous disease that can be treated by using pharmacologic approaches (e.g., dopamine agonists
and levodopa) and nonpharmacologic approaches (e.g., music), based on symptoms and progression level in patients. Even
though current treatments have demonstrated effectiveness, clinical challenges remain because the BBB reduces medication
received and lowers the efficacy of drug delivery, which impairs the treatment’s effect. Therefore, EVs, as an emerging
delivery platform, are highly promising for PD treatment since they can readily cross the BBB with high therapeutic
efficiency through the loading or functionalization process. However, defining a safe source of EVs, reliably purifying and
isolating EVs with high yield, and improving the efficacy of therapeutic loading in EVs remain challenging in this field.
Therefore, future investigations should focus on generating large-scale exosomal carriers and designing new effective drugs
encapsulated in EVs for better efficacy.
Extracellular vesicles as a next-generation drug delivery platform
