Plain-language summary
Neurodegenerative conditions such as Alzheimer's disease, Parkinson's disease and multiple sclerosis affect cognition, mood and movement, and small-molecule drugs still struggle to reach the brain because the blood-brain barrier keeps most of them out. This review argues that exosomes - natural 30-150 nm vesicles released by mesenchymal stem cells, neural stem cells and immune cells - are unusually well suited to the job. They provoke little immune reaction, carry proteins, mRNA and miRNA, and appear able to cross the barrier themselves. The authors summarise how exosomes are classified, isolated and characterised, how drugs can be loaded into them, and how the main routes of administration compare. They give particular attention to intranasal delivery, which carries material from the nose to the brain along the olfactory and trigeminal nerves without surgery and with limited systemic exposure. Evidence from Alzheimer's, Parkinson's and multiple sclerosis models, together with the first clinical studies, is reviewed alongside the open questions: whether exosomes help or harm barrier function, and how to achieve GMP-grade production, consistent dosing and the large placebo-controlled trials still needed.
Key findings
- The blood-brain barrier limits central nervous system exposure to small-molecule drugs, which is the main driver behind interest in biological carriers such as exosomes.
- Exosomes are 30-150 nm vesicles from mesenchymal stem cells, neural stem cells and immune cells, and their low immunogenicity, biocompatibility and cargo capacity make them attractive drug carriers.
- The review compares intravenous, intracerebral, intrathecal, intra-arterial and intranasal administration, and singles out the intranasal route for its non-invasive nose-to-brain access via the olfactory and trigeminal nerves.
- Preclinical and early clinical evidence in Alzheimer's disease, Parkinson's disease and multiple sclerosis is encouraging, but GMP-grade scale-up, consistent particle-based dosing benchmarks and large placebo-controlled trials remain outstanding.
Original abstract
Neurodegenerative disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), and Multiple Sclerosis (MS), represent a substantial and growing global health burden, collectively accounting for millions of disability-adjusted life years (DALYs) worldwide and severely impacting cognition, mood, behavior, and motor function. Current therapies, particularly small-molecule drugs, are challenged by the blood-brain barrier (BBB), resulting in poor central nervous system (CNS) bioavailability, systemic adverse effects, and suboptimal patient adherence, underscoring the urgent need for novel delivery platforms. Exosomes, endogenous nanoscale extracellular vesicles (30-150 nm) derived from sources such as mesenchymal stem cells, neural stem cells, and immune cells, have emerged as highly promising biogenic drug carriers owing to their low immunogenicity, inherent biocompatibility, cargo versatility (proteins, mRNA, miRNA), and unique innate ability to cross the BBB, positioning them as superior alternatives to synthetic nanocarriers such as liposomes, niosomes, and solid lipid nanoparticles for targeted CNS delivery. This review provides a comprehensive overview of exosome biology and therapeutics for AD, PD, and MS, covering classification, isolation and characterization methods, drug-loading strategies and a comparative analysis of administration routes (intravenous, intracerebral, intrathecal, intra-arterial, and intranasal). Particular emphasis is placed on the intranasal route, which offers a non-invasive, direct nose-to-brain pathway via the olfactory and trigeminal nerves, effectively bypassing the BBB while minimizing systemic exposure. The review also examines the dual therapeutic and pathological roles of exosomes in BBB function, and emphasizes preclinical and early clinical evidence across AD, PD, and MS. Finally, the review outlines the major manufacturing, regulatory, and standardization hurdles that must be addressed including GMP-grade scale-up, consistent particle-based dosing benchmarks, and large placebo-controlled trials before intranasal exosome therapeutics can progress from promising preclinical candidates to approved disease-modifying treatments for neurodegenerative disorders.
Frequently asked questions
What did this study find?
Neurodegenerative conditions such as Alzheimer's disease, Parkinson's disease and multiple sclerosis affect cognition, mood and movement, and small-molecule drugs still struggle to reach the brain because the blood-brain barrier keeps most of them out. This review argues that exosomes - natural 30-150 nm vesicles released by mesenchymal stem cells, neural stem cells and immune cells - are unusually well suited to the job. They provoke little immune reaction, carry proteins, mRNA and miRNA, and appear able to cross the barrier themselves. The authors summarise how exosomes are classified, isolated and characterised, how drugs can be loaded into them, and how the main routes of administration compare. They give particular attention to intranasal delivery, which carries material from the nose to the brain along the olfactory and trigeminal nerves without surgery and with limited systemic exposure. Evidence from Alzheimer's, Parkinson's and multiple sclerosis models, together with the first clinical studies, is reviewed alongside the open questions: whether exosomes help or harm barrier function, and how to achieve GMP-grade production, consistent dosing and the large placebo-controlled trials still needed.
Was this tested in humans or in the laboratory?
This is a review: it summarises and weighs up previously published studies rather than presenting new experiments.
Where can I read the original paper?
The full text lives with the publisher: https://doi.org/10.1016/j.bbrc.2026.154474
How to cite this paper
Hirlekar Rajashree, Agnihotri Srushti, Sathe Shalom, Nagarsenkar Mangal. Exosomal innovations in neurodegenerative disorders: Emerging insights and intranasal route.. Biochemical and biophysical research communications. 2026, 2026-08-28. DOI: 10.1016/j.bbrc.2026.154474
Source & verification
- Journal: Biochemical and biophysical research communications
- Published: 28 August 2026
- DOI: 10.1016/j.bbrc.2026.154474
- PubMed ID: 42664828
- Indexed via: pubmed
- MeSH terms: Humans, Exosomes, Administration, Intranasal, Neurodegenerative Diseases, Animals, Blood-Brain Barrier, Drug Delivery Systems, Drug Carriers