life sciences
Exosomes as Drug Delivery Vehicles for Parkinson’s Disease Therapy Diane Youngstrom Exosomes are the epitome of “small but mighty.” They have the potential to revolutionize drug delivery by allowing impermeable compounds to cross the blood brain barrier (BBB). Exosomes are effective Dr. Elena Batrakova drug carriers because they are exceedingly small – nanosized, in fact (see Figure 1) – and because they have multiple adhesive proteins on their surface that facilitate their specialization in cell-to-cell communication by binding to their targets. In addition, exosomes have plenty of interior space to house compounds of interest.1 Dr. Batrakova – a research associate professor at the Eshelman School of Pharmacy – and her collaborators have used exosome-based drug formulations to treat cancer, HIV, infectious diseases, inflammatory disorders, and neurodegenerative diseases like Parkinson’s disease and Alzheimer’s disease. According to Dr. Batrakova, crossing the BBB is one of the foremost obstacles in drug delivery because “the brain is like a sanctuary.”2 Pathogens in the bloodstream are thwarted by the BBB due to its high selectivity for what it allows to pass into the brain. While the selective nature of the BBB protects a healthy brain, it also prevents drugs from helping a sick brain. Thus, developing innovative mechanisms to cross the BBB is crucial for the advancement of treatments for neurodegenerative diseases and other pathologies. Exosomes are an exciting frontier in drug delivery. Similar to how Uber Eats uses an address to deliver food to a customer, exosomes provide a biological address to deliver drugs to specific locations in the brain and body. Exosomes have a natural lipid bilayer with many adhesive proteins on their surface, which facilitate the binding of exosomes to their target cells, as well as a roomy interior that can be packed with drug therapies to be carried across the BBB.3 Exosome treatments are based on the natural communication mechanisms of our body used to deliver proteins or genes to
Figure 1: Exosome size compared to the average cell, bacteria, and virus. Figure courtesy of Nina Koliha
other cells and organs. Batrakova’s lab decided to “use macrophages as smart vehicles because if you load them with nanoparticles they know where to go”.2 Macrophages are a type of white blood cell that devour foreign materials to protect the body, and are instrumental to natural immune responses. Equipping macrophages with exosomes harnesses the body’s immune system and bolsters the body’s ability to fight diseases. The exosomes from macrophages travel to sites of inflammation, unzipping the tight barriers of the BBB (see Figure 2). Because exosomes are naturally produced by many cells in the body, they are better than previous methods at interacting with target cells for more selective drug delivery. The unique proteins and lipids on the surface membrane of exosomes allow them to communicate with neighboring cells and cells in distant systems. In addition, exosomes are less likely to be filtered out by the liver and spleen because immune cells – such as macrophages – recognize them as non-pathogenic, which leads to decreased exosome degradation. Therefore, more of the drug injected via exosomes will be available for combating disease. In general, increasing bioavailability inherently lowers the cost of treatment, and reduces the risk of side effects, because less of the compound is required. After researchers determined the superiority of
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