Exosomes as drug delivery vehicles for Parkinson’s disease therapy
Open accessAbstract
Exosomes are naturally occurring nanosized vesicles that have attracted considerable attention as drug delivery vehicles in the past few years. Exosomes are comprised of natural lipid bilayers with the abundance of adhesive proteins that readily interact with cellular membranes. We posit that exosomes secreted by monocytes and macrophages can provide an unprecedented opportunity to avoid entrapment in mononuclear phagocytes (as a part of the host immune system), and at the same time enhance delivery of incorporated drugs to target cells ultimately increasing drug therapeutic efficacy. In light of this, we developed a new exosomal-based delivery system for a potent antioxidant, catalase, to treat Parkinson's disease (PD). Catalase was loaded into exosomes ex vivo using different methods: the incubation at room temperature, permeabilization with saponin, freeze-thaw cycles, sonication, or extrusion. The size of the obtained catalase-loaded exosomes (exoCAT) was in the range of 100-200nm. A reformation of exosomes upon sonication and extrusion, or permeabilization with saponin resulted in high loading efficiency, sustained release, and catalase preservation against proteases degradation. Exosomes were readily taken up by neuronal cells in vitro. A considerable amount of exosomes was detected in PD mouse brain following intranasal administration. ExoCAT provided significant neuroprotective effects in in vitro and in vivo models of PD. Overall, exosome-based catalase formulations have a potential to be a versatile strategy to treat inflammatory and neurodegenerative disorders.
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Extracellular vesicles have been used to transfer Parkinson's disease-specific drugs targeting dopaminergic neurons.
“As a result, EVs have been used to transfer PD-specific drugs, specifically targeting dopaminergic neurons [245].”
From The Impact of Neurotoxin Proteins Trafficked by Primary Cilia and Extracellular Vesicles in Neurodegenerative Diseases (2025) · cites this paper as [245]
The Results (§3.3 and §3.5; page unavailable) describe catalase-loaded exosomes used in Parkinson’s disease models and report protection of dopaminergic neurons. But §3.6 reports exosome accumulation in neurons, microglia, and some endothelial cells, not specific targeting of dopaminergic neurons. (LLM, conf=0.85)
Experimental — accuracy not yet measuredExosomes have been tested in preclinical models for delivering proteins and small RNA across the BBB.
“In addition, exosomes have also been tested in preclinical models for delivering proteins and small RNA across the BBB (16, 235, 323).”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [235]
The Introduction reports exosome-mediated siRNA delivery across biological barriers with improved brain delivery, and the Results and Conclusion describe catalase-loaded exosomes delivering a therapeutic protein in a mouse Parkinson’s model. However, the catalase treatment was given intranasally; the Discussion says this route can bypass the BBB, so the paper does not establish that the protein was delivered across it. Page numbers are unavailable in our copy. (LLM, conf=0.85)
Experimental — accuracy not yet measuredExoCAT showed effective neuroprotection in vivo models of Parkinson's disease.
“In addition, ExoCAT showed effective neuroprotection in vivo models of PD [75].”
From The Therapeutic Potential and Clinical Significance of Exosomes as Carriers of Drug Delivery System (2022) · cites this paper as [75]
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“This finding is also beneficial for the treatment of exosomes, considering that endogenous antioxidants, such as catalase, can be delivered directly through exosomes [76].”
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“Furthermore, because they can carry various molecules, exosomes are now being tested as drug carriers to treat diseases such as Parkinson disease [36], pancreatic cancers [37] and lung diseases [38].”
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“As a result, EVs have been used to transfer PD-specific drugs, specifically targeting dopaminergic neurons [245].”
- Authors
- Haney, M. J., Klyachko, N. L., Zhao, Y., Gupta, R., Plotnikova, E. G., He, Z., Patel, T., Piroyan, A., Sokolsky, M., Kabanov, A. V., & Batrakova, E. V.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- Lomonosov Moscow State University (RU)
- Corresponding author
- Batrakova, Elena V.
- ORCID
- Venue
- Journal of Controlled Release
- Publisher
- Elsevier BV
- Published
- 2015-06
- Volume
- 207
- Pages
- 18-30
- ISSN
- 0168-3659 (ISSN-L)
- PMC
- PMC4430381
- OpenAlex
- W2091250479
- Cited by
- 2,009
- References
- 93
- Citations by year
- 2026: 156 · 2025: 221 · 2024: 263 · 2023: 271 · 2022: 232 · 2021: 252 · 2020: 209 · 2019: 151 · 2018: 102 · 2017: 82 · 2016: 53 · 2015: 15 · 2014: 1
- FWCI
- 36.26
- Type
- journal article
- Language
- en
- Update notices
- erratum (2021-11-10)
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Controlled Release (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- UNC Libraries
- Funders
- National Institutes of Health (1RO1 NS057748, RR021937)
- Ministry of Education and Science of the Russian Federation
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Keywords
- exosomes, drug carriers, Parkinson's disease, catalase, antioxidant therapy, sonication, extrusion, saponin permeabilization, freeze-thaw cycles, neuroprotection, intranasal administration, neurodegenerative diseases, monocytes/macrophages
- MeSH terms
- RAW 264.7 Cells, Administration, Intranasal, Animals, Anti-Inflammatory Agents, Antioxidants, Antiparkinson Agents, Brain, Catalase, Chemistry, Pharmaceutical, Disease Models, Animal, Drug Carriers, Female, Kinetics, Mice, Inbred C57BL, Neurons, Solubility, Technology, Pharmaceutical, Oxidopamine, PC12 Cells, Oxidative Stress, Neuroprotective Agents, Parkinsonian Disorders, Nanomedicine, Mice, Rats, Nanoparticles, Exosomes
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