---
title: "Exosomal Drug Delivery for Neurodegenerative Diseases: Intranasal Route and Therapeutic Insights"
id: "pubmed-42664828"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42664828"
content_type: "clinical_feed_article"
specialty: "Pharmacology"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42664828/"
doi: "10.1016/j.bbrc.2026.154474"
published_at: "2026-10-08T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Exosomal Drug Delivery for Neurodegenerative Diseases: Intranasal Route and Therapeutic Insights
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42664828
- **Specialty:** [Pharmacology](https://medichelpline.com/clinical-feed/pharmacology.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42664828/)
- **DOI:** [10.1016/j.bbrc.2026.154474](https://doi.org/10.1016%2Fj.bbrc.2026.154474)
- **Published At:** 2026-10-08T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- Neurodegenerative disorders such as **Alzheimer's disease**, **Parkinson's disease**, and **Multiple Sclerosis** impose a large global burden, affecting cognition, mood, behavior, and motor function and contributing substantial DALYs. - Existing small-molecule therapies are limited by the **blood-brain barrier** (BBB), producing poor CNS bioavailability, systemic adverse effects, and adherence problems, motivating new delivery platforms. - **Exosomes** are endogenous extracellular vesicles (30–150 nm) from mesenchymal stem cells, neural stem cells, and immune cells that show low immunogenicity, biocompatibility, and cargo versatility (proteins, mRNA, miRNA). - Exosomes possess an innate ability to cross the **BBB**, making them promising alternatives to synthetic nanocarriers (liposomes, niosomes, solid lipid nanoparticles) for targeted CNS delivery. - The review summarizes exosome classification, methods for isolation and characterization, and drug-loading strategies, noting their broad cargo capacity and engineering potential. - Multiple administration routes are compared: intravenous, intracerebral, intrathecal, intra-arterial, and particularly **intranasal**, which provides a noninvasive nose-to-brain pathway via the olfactory and trigeminal nerves and reduces systemic exposure. - Exosomes have dual roles: therapeutic potential for delivering disease-modifying cargo and possible pathological contributions to BBB dysfunction; both aspects are examined. - Preclinical and early clinical evidence across AD, PD, and MS supports exosome utility but remains at an early stage; specifics of individual studies were not detailed in the abstract. - Significant translational hurdles remain, including GMP-scale manufacturing, establishing consistent particle-based dosing metrics, regulatory standardization, and the need for large, placebo-controlled clinical trials before intranasal exosome therapies can reach approval. - The authors declare no competing interests and note that this review received no specific grant funding.
## Clinical Analysis & Structured Key Points
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Epub 2026 Aug 21. # Exosomal innovations in neurodegenerative disorders: Emerging insights and intranasal route [Rajashree Hirlekar](https://pubmed.ncbi.nlm.nih.gov/?term=Hirlekar+R&cauthor_id=42664828)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42664828/#full-view-affiliation-1 "Vivekanand Education Society's College of Pharmacy, HAMC, Mumbai, 400074, India. Electronic address: rajashree.hirlekar@ves.ac.in."), [Srushti Agnihotri](https://pubmed.ncbi.nlm.nih.gov/?term=Agnihotri+S&cauthor_id=42664828)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42664828/#full-view-affiliation-2 "Vivekanand Education Society's College of Pharmacy, HAMC, Mumbai, 400074, India. Electronic address: srushti.agnihotribp2022@ves.ac.in."), [Shalom Sathe](https://pubmed.ncbi.nlm.nih.gov/?term=Sathe+S&cauthor_id=42664828)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42664828/#full-view-affiliation-3 "Vivekanand Education Society's College of Pharmacy, HAMC, Mumbai, 400074, India. Electronic address: shalom.sathebp2022@ves.ac.in."), [Mangal Nagarsenkar](https://pubmed.ncbi.nlm.nih.gov/?term=Nagarsenkar+M&cauthor_id=42664828)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42664828/#full-view-affiliation-4 "Vivekanand Education Society's College of Pharmacy, HAMC, Mumbai, 400074, India. Electronic address: mangal.nagarsenker@gmail.com.") Affiliations Expand ### Affiliations * 1 Vivekanand Education Society's College of Pharmacy, HAMC, Mumbai, 400074, India. Electronic address: rajashree.hirlekar@ves.ac.in. * 2 Vivekanand Education Society's College of Pharmacy, HAMC, Mumbai, 400074, India. Electronic address: srushti.agnihotribp2022@ves.ac.in. * 3 Vivekanand Education Society's College of Pharmacy, HAMC, Mumbai, 400074, India. Electronic address: shalom.sathebp2022@ves.ac.in. * 4 Vivekanand Education Society's College of Pharmacy, HAMC, Mumbai, 400074, India. Electronic address: mangal.nagarsenker@gmail.com. * PMID: **42664828** * DOI: [ 10.1016/j.bbrc.2026.154474 ](https://doi.org/10.1016/j.bbrc.2026.154474) Item in Clipboard Review # Exosomal innovations in neurodegenerative disorders: Emerging insights and intranasal route Rajashree Hirlekar et al. Biochem Biophys Res Commun. 2026. Show details Display options Display options Format Abstract PubMed PMID Biochem Biophys Res Commun Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Biochem+Biophys+Res+Commun%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Biochem+Biophys+Res+Commun%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42664828/) . 2026 Oct 8:834:154474. doi: 10.1016/j.bbrc.2026.154474. Epub 2026 Aug 21. ### Authors [Rajashree Hirlekar](https://pubmed.ncbi.nlm.nih.gov/?term=Hirlekar+R&cauthor_id=42664828)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42664828/#short-view-affiliation-1 "Vivekanand Education Society's College of Pharmacy, HAMC, Mumbai, 400074, India. Electronic address: rajashree.hirlekar@ves.ac.in."), [Srushti Agnihotri](https://pubmed.ncbi.nlm.nih.gov/?term=Agnihotri+S&cauthor_id=42664828)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42664828/#short-view-affiliation-2 "Vivekanand Education Society's College of Pharmacy, HAMC, Mumbai, 400074, India. Electronic address: srushti.agnihotribp2022@ves.ac.in."), [Shalom Sathe](https://pubmed.ncbi.nlm.nih.gov/?term=Sathe+S&cauthor_id=42664828)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42664828/#short-view-affiliation-3 "Vivekanand Education Society's College of Pharmacy, HAMC, Mumbai, 400074, India. Electronic address: shalom.sathebp2022@ves.ac.in."), [Mangal Nagarsenkar](https://pubmed.ncbi.nlm.nih.gov/?term=Nagarsenkar+M&cauthor_id=42664828)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42664828/#short-view-affiliation-4 "Vivekanand Education Society's College of Pharmacy, HAMC, Mumbai, 400074, India. Electronic address: mangal.nagarsenker@gmail.com.") ### Affiliations * 1 Vivekanand Education Society's College of Pharmacy, HAMC, Mumbai, 400074, India. Electronic address: rajashree.hirlekar@ves.ac.in. * 2 Vivekanand Education Society's College of Pharmacy, HAMC, Mumbai, 400074, India. Electronic address: srushti.agnihotribp2022@ves.ac.in. * 3 Vivekanand Education Society's College of Pharmacy, HAMC, Mumbai, 400074, India. Electronic address: shalom.sathebp2022@ves.ac.in. * 4 Vivekanand Education Society's College of Pharmacy, HAMC, Mumbai, 400074, India. Electronic address: mangal.nagarsenker@gmail.com. * PMID: **42664828** * DOI: [ 10.1016/j.bbrc.2026.154474 ](https://doi.org/10.1016/j.bbrc.2026.154474) Item in Clipboard Full text links Cite Display options Display options Format Abstract PubMed PMID Linked Discoveries ## 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. **Keywords:** Blood-brain barrier; Exosomes; Intranasal drug delivery; Neurodegenerative diseases; Targeted drug delivery. Copyright © 2026 Elsevier Inc. All rights reserved. [PubMed Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) ## Conflict of interest statement Declaration of competing interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. This review work did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. ## Similar articles * [ Exosome-based nanomedicine for neurological disorders: mechanisms, engineering, and therapeutic potential. ](https://pubmed.ncbi.nlm.nih.gov/42576814/) Singh N, Guha L, Kumari A.Singh N, et al.Ther Deliv. 2026 Jul;17(7):719-758. doi: 10.1080/20415990.2026.2715878. Epub 2026 Aug 11.Ther Deliv. 2026.PMID: 42576814Review. * [ Nanocarriers in Alzheimer's Therapy: A Comprehensive Review on Nanoparticulate Drug Delivery Systems. ](https://pubmed.ncbi.nlm.nih.gov/41930767/) Parashar AK, Saraogi GK, Sethi VA, Yasin HKA.Parashar AK, et al.Curr Neurovasc Res. 2026;23(3):160-173. doi: 10.2174/0115672026435071260129105648.Curr Neurovasc Res. 2026.PMID: 41930767Review. * [ Engineering exosomes for targeted neurodegenerative therapy: innovations in biogenesis, drug loading, and clinical translation. ](https://pubmed.ncbi.nlm.nih.gov/41328354/) Huang Q, Wang S, Liu Z, Rao L, Cheng K, Mao X.Huang Q, et al.Theranostics. 2026 Jan 1;16(1):545-579. doi: 10.7150/thno.117143. eCollection 2026.Theranostics. 2026.PMID: 41328354Free PMC article.Review. * [ Large-Scale Production and Therapeutic Evaluation of Exosomes for Cancer Treatment. ](https://pubmed.ncbi.nlm.nih.gov/41340272/) Kimiz-Gebologlu I, Oncel SS.Kimiz-Gebologlu I, et al.Thorac Res Pract. 2025 Dec 1;26(Suppl 1):28-30. doi: 10.4274/ThoracResPract.2025.s011.Thorac Res Pract. 2025.PMID: 41340272Free PMC article. * [ Convolutions in the rendition of nose to brain therapeutics from bench to bedside: Feats & fallacies. ](https://pubmed.ncbi.nlm.nih.gov/34906605/) Goel H, Kalra V, Verma SK, Dubey SK, Tiwary AK.Goel H, et al.J Control Release. 2022 Jan;341:782-811. doi: 10.1016/j.jconrel.2021.12.009. Epub 2021 Dec 11.J Control Release. 2022.PMID: 34906605Review. 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