---
title: "Chitosan-based hydrogels for intranasal drug delivery in brain disease treatment"
id: "pubmed-42537824"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42537824"
content_type: "clinical_feed_article"
specialty: "Pharmacology"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42537824/"
doi: "10.1016/j.ijpharm.2026.127259"
published_at: "2026-09-05T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Chitosan-based hydrogels for intranasal drug delivery in brain disease treatment
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42537824
- **Specialty:** [Pharmacology](https://medichelpline.com/clinical-feed/pharmacology.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42537824/)
- **DOI:** [10.1016/j.ijpharm.2026.127259](https://doi.org/10.1016%2Fj.ijpharm.2026.127259)
- **Published At:** 2026-09-05T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- Neurodegenerative and other brain diseases pose increasing public health challenges because effective delivery of therapeutics to the central nervous system (CNS) is limited by the **blood-brain barrier (BBB)**. - Noninvasive strategies such as **intranasal (IN)** administration and nanoscale delivery systems are under active investigation to improve brain targeting and patient acceptability. - IN administration enables direct nose-to-brain transport mainly via the **olfactory pathway**, with the trigeminal route as an additional conduit. - **Chitosan (CS)-based hydrogels** have attracted attention for IN delivery due to **biocompatibility**, **biodegradability**, and **mucoadhesive** properties that prolong nasal residence time. - CS hydrogels can transiently modulate epithelial tight junctions and enhance drug permeation across nasal epithelium, supporting improved CNS uptake. - Recent work summarized in the review examines CS-based IN hydrogels applied to multiple brain conditions: **Alzheimer’s disease (AD)**, **Parkinson’s disease (PD)**, depressive disorders, ischemia, brain tumors, epilepsy and seizures, and schizophrenia. - The review analyzes relationships between **hydrogel design** (formulation attributes) and therapeutic performance in preclinical settings, emphasizing how material properties influence residence time, permeation, and drug release. - Translational challenges identified include moving formulations from bench to bedside, regulatory and clinical development hurdles, and the need for standardized evaluation metrics; the review outlines future perspectives for clinical development of CS-based IN hydrogel systems. - The authors declare no competing financial interests or personal relationships that influenced the work.
## Clinical Analysis & Structured Key Points
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Epub 2026 Jul 31. # Chitosan-based hydrogel for intranasal drug delivery; current advances in the brain diseases treatment [Omar Abouali](https://pubmed.ncbi.nlm.nih.gov/?term=Abouali+O&cauthor_id=42537824)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42537824/#full-view-affiliation-1 "Faculty of Pharmacy, Cyprus International University, Nicosia, Cyprus."), [Aysan Mokabber](https://pubmed.ncbi.nlm.nih.gov/?term=Mokabber+A&cauthor_id=42537824)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42537824/#full-view-affiliation-2 "Faculty of Medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran."), [Saghi Naderpour](https://pubmed.ncbi.nlm.nih.gov/?term=Naderpour+S&cauthor_id=42537824)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42537824/#full-view-affiliation-3 "Functional Neurosurgery Research Center, Shohada Tajrish Comprehensive Neurosurgical Center of Excellence, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Faculty of Pharmacy, Eastern Mediterranean University Famagusta, North Cyprus via Mersin 10, Turkey."), [Elham Vojoudi](https://pubmed.ncbi.nlm.nih.gov/?term=Vojoudi+E&cauthor_id=42537824)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42537824/#full-view-affiliation-4 "Mehr Fertility Research Center, Mehr Outpatient Surgical and Infertility Center, Guilan University of Medical Sciences, Rasht, Iran."), [Farshid Sefat](https://pubmed.ncbi.nlm.nih.gov/?term=Sefat+F&cauthor_id=42537824)[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42537824/#full-view-affiliation-5 "Department of Bio-medical and Electronics Engineering, School of Engineering, University of Bradford, Bradford, UK; Interdisciplinary Research Center in Polymer Science & Technology \(Polymer IRC\), University of Bradford, Bradford, UK."), [Morvarid Saeinasab](https://pubmed.ncbi.nlm.nih.gov/?term=Saeinasab+M&cauthor_id=42537824)[ 6 ](https://pubmed.ncbi.nlm.nih.gov/42537824/#full-view-affiliation-6 "Department of Bio-medical and Electronics Engineering, School of Engineering, University of Bradford, Bradford, UK; Faculty of Biology Medicine and Health, University of Manchester, Manchester, UK."), [Milad Rahimzadegan](https://pubmed.ncbi.nlm.nih.gov/?term=Rahimzadegan+M&cauthor_id=42537824)[ 7 ](https://pubmed.ncbi.nlm.nih.gov/42537824/#full-view-affiliation-7 "Functional Neurosurgery Research Center, Shohada Tajrish Comprehensive Neurosurgical Center of Excellence, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address: milad.rahimzadegan@gmail.com."), [Rahim Nosrati](https://pubmed.ncbi.nlm.nih.gov/?term=Nosrati+R&cauthor_id=42537824)[ 8 ](https://pubmed.ncbi.nlm.nih.gov/42537824/#full-view-affiliation-8 "Cellular and Molecular Research Center, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran. Electronic address: Rahim_nosrati@gums.ac.ir.") Affiliations Expand ### Affiliations * 1 Faculty of Pharmacy, Cyprus International University, Nicosia, Cyprus. * 2 Faculty of Medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran. * 3 Functional Neurosurgery Research Center, Shohada Tajrish Comprehensive Neurosurgical Center of Excellence, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Faculty of Pharmacy, Eastern Mediterranean University Famagusta, North Cyprus via Mersin 10, Turkey. * 4 Mehr Fertility Research Center, Mehr Outpatient Surgical and Infertility Center, Guilan University of Medical Sciences, Rasht, Iran. * 5 Department of Bio-medical and Electronics Engineering, School of Engineering, University of Bradford, Bradford, UK; Interdisciplinary Research Center in Polymer Science & Technology (Polymer IRC), University of Bradford, Bradford, UK. * 6 Department of Bio-medical and Electronics Engineering, School of Engineering, University of Bradford, Bradford, UK; Faculty of Biology Medicine and Health, University of Manchester, Manchester, UK. * 7 Functional Neurosurgery Research Center, Shohada Tajrish Comprehensive Neurosurgical Center of Excellence, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address: milad.rahimzadegan@gmail.com. * 8 Cellular and Molecular Research Center, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran. Electronic address: Rahim_nosrati@gums.ac.ir. * PMID: **42537824** * DOI: [ 10.1016/j.ijpharm.2026.127259 ](https://doi.org/10.1016/j.ijpharm.2026.127259) Item in Clipboard Review # Chitosan-based hydrogel for intranasal drug delivery; current advances in the brain diseases treatment Omar Abouali et al. Int J Pharm. 2026. Show details Display options Display options Format Abstract PubMed PMID Int J Pharm Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Int+J+Pharm%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Int+J+Pharm%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42537824/) . 2026 Sep 5:702:127259. doi: 10.1016/j.ijpharm.2026.127259. Epub 2026 Jul 31. ### Authors [Omar Abouali](https://pubmed.ncbi.nlm.nih.gov/?term=Abouali+O&cauthor_id=42537824)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42537824/#short-view-affiliation-1 "Faculty of Pharmacy, Cyprus International University, Nicosia, Cyprus."), [Aysan Mokabber](https://pubmed.ncbi.nlm.nih.gov/?term=Mokabber+A&cauthor_id=42537824)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42537824/#short-view-affiliation-2 "Faculty of Medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran."), [Saghi Naderpour](https://pubmed.ncbi.nlm.nih.gov/?term=Naderpour+S&cauthor_id=42537824)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42537824/#short-view-affiliation-3 "Functional Neurosurgery Research Center, Shohada Tajrish Comprehensive Neurosurgical Center of Excellence, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Faculty of Pharmacy, Eastern Mediterranean University Famagusta, North Cyprus via Mersin 10, Turkey."), [Elham Vojoudi](https://pubmed.ncbi.nlm.nih.gov/?term=Vojoudi+E&cauthor_id=42537824)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42537824/#short-view-affiliation-4 "Mehr Fertility Research Center, Mehr Outpatient Surgical and Infertility Center, Guilan University of Medical Sciences, Rasht, Iran."), [Farshid Sefat](https://pubmed.ncbi.nlm.nih.gov/?term=Sefat+F&cauthor_id=42537824)[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42537824/#short-view-affiliation-5 "Department of Bio-medical and Electronics Engineering, School of Engineering, University of Bradford, Bradford, UK; Interdisciplinary Research Center in Polymer Science & Technology \(Polymer IRC\), University of Bradford, Bradford, UK."), [Morvarid Saeinasab](https://pubmed.ncbi.nlm.nih.gov/?term=Saeinasab+M&cauthor_id=42537824)[ 6 ](https://pubmed.ncbi.nlm.nih.gov/42537824/#short-view-affiliation-6 "Department of Bio-medical and Electronics Engineering, School of Engineering, University of Bradford, Bradford, UK; Faculty of Biology Medicine and Health, University of Manchester, Manchester, UK."), [Milad Rahimzadegan](https://pubmed.ncbi.nlm.nih.gov/?term=Rahimzadegan+M&cauthor_id=42537824)[ 7 ](https://pubmed.ncbi.nlm.nih.gov/42537824/#short-view-affiliation-7 "Functional Neurosurgery Research Center, Shohada Tajrish Comprehensive Neurosurgical Center of Excellence, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address: milad.rahimzadegan@gmail.com."), [Rahim Nosrati](https://pubmed.ncbi.nlm.nih.gov/?term=Nosrati+R&cauthor_id=42537824)[ 8 ](https://pubmed.ncbi.nlm.nih.gov/42537824/#short-view-affiliation-8 "Cellular and Molecular Research Center, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran. Electronic address: Rahim_nosrati@gums.ac.ir.") ### Affiliations * 1 Faculty of Pharmacy, Cyprus International University, Nicosia, Cyprus. * 2 Faculty of Medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran. * 3 Functional Neurosurgery Research Center, Shohada Tajrish Comprehensive Neurosurgical Center of Excellence, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Faculty of Pharmacy, Eastern Mediterranean University Famagusta, North Cyprus via Mersin 10, Turkey. * 4 Mehr Fertility Research Center, Mehr Outpatient Surgical and Infertility Center, Guilan University of Medical Sciences, Rasht, Iran. * 5 Department of Bio-medical and Electronics Engineering, School of Engineering, University of Bradford, Bradford, UK; Interdisciplinary Research Center in Polymer Science & Technology (Polymer IRC), University of Bradford, Bradford, UK. * 6 Department of Bio-medical and Electronics Engineering, School of Engineering, University of Bradford, Bradford, UK; Faculty of Biology Medicine and Health, University of Manchester, Manchester, UK. * 7 Functional Neurosurgery Research Center, Shohada Tajrish Comprehensive Neurosurgical Center of Excellence, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address: milad.rahimzadegan@gmail.com. * 8 Cellular and Molecular Research Center, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran. Electronic address: Rahim_nosrati@gums.ac.ir. * PMID: **42537824** * DOI: [ 10.1016/j.ijpharm.2026.127259 ](https://doi.org/10.1016/j.ijpharm.2026.127259) Item in Clipboard Full text links Cite Display options Display options Format Abstract PubMed PMID ## Abstract Neurodegenerative diseases represent a growing health concern that is projected to become more prevalent and affect more people in the upcoming decades. One of the most complicated components of recent neurodegenerative disease therapies is the penetration and delivery of therapeutics to the central nervous system (CNS), which are hindered via the blood-brain barrier (BBB). In response, innovative treatment approaches leveraging noninvasive techniques including nanosized drug delivery systems and intranasal (IN) administration with higher treatment efficacy and patient satisfaction are developing as potential options. IN administration delivers medications directly to the brain through both the olfactory and trigeminal pathways, with the olfactory pathway representing the primary route for nose-to-brain transport. Among various IN platforms, chitosan (CS)-based hydrogels have attracted considerable attention because of their excellent biocompatibility, biodegradability, mucoadhesive properties, and ability to enhance drug permeation by prolonging nasal residence time and transiently modulating epithelial tight junctions. This review critically summarizes recent advances in CS-based hydrogels for IN drug delivery for the treatment of brain diseases including Alzheimer's disease (AD), Parkinson's disease (PD), depressive manifestations, ischemia,brain tumors,epilepsy, seizures, and schizophrenia. In addition, the review discusses the relationships between hydrogel design and therapeutic performance, highlights current translational challenges, and outlines future perspectives for the clinical development of CS-based IN hydrogel systems. **Keywords:** Chitosan; Drug delivery; Hydrogel; Intranasal; Neurodegenerative diseases. Copyright © 2026 Elsevier B.V. All rights reserved. [PubMed Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) ## Conflict of interest statement Declaration of competing interest 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. ## Similar articles * [ Chitosan nanoparticles for brain targeted nose-to-brain drug delivery in neurodegenerative disease: a comprehensive exploration of advances, limitations and future prospects. ](https://pubmed.ncbi.nlm.nih.gov/41582778/) Mumtaz, Unnithan D, Hosseini H, Ali J, Khan MA.Mumtaz, et al.Expert Opin Drug Deliv. 2026 May;23(5):761-779. doi: 10.1080/17425247.2026.2619090. Epub 2026 Jan 29.Expert Opin Drug Deliv. 2026.PMID: 41582778Review. * [ Chitosan-Based Nanoparticles for Nose-to-Brain Drug Delivery: A Real Path toward Effective CNS Therapy? ](https://pubmed.ncbi.nlm.nih.gov/42024000/) Riani LR, Seno GFB, Silva DM, Toledo CR, Paiva MRB, Santos JS, Fabri RL, Pittella F, Tavares GD.Riani LR, et al.ACS Biomater Sci Eng. 2026 May 11;12(5):2567-2589. doi: 10.1021/acsbiomaterials.6c00137. Epub 2026 Apr 23.ACS Biomater Sci Eng. 2026.PMID: 42024000Free PMC article.Review. * [ Intranasal delivery of lipid-based nanoparticles for the treatment of neurodegenerative diseases: advances, challenges and future perspectives. ](https://pubmed.ncbi.nlm.nih.gov/41206776/) Mulet I Piera X, Del Campo-Montoya R, Cuadrado-Tejedor M, Garcia-Osta A, Garbayo E, Blanco-Prieto MJ.Mulet I Piera X, et al.Expert Opin Drug Deliv. 2026 Feb;23(2):333-351. doi: 10.1080/17425247.2025.2587903. Epub 2025 Nov 14.Expert Opin Drug Deliv. 2026.PMID: 41206776Review. * [ Strategies to improve nasal administration of antiretroviral therapeutics for the treatment of NeuroAIDS. ](https://pubmed.ncbi.nlm.nih.gov/41518071/) Bazargani A, Duong K, Hejazi M, Golshahi L.Bazargani A, et al.Ther Deliv. 2025 Dec;16(12):1225-1243. doi: 10.1080/20415990.2025.2610208. Epub 2026 Jan 10.Ther Deliv. 2025.PMID: 41518071Review. * [ Convolutions in the rendition of nose to brain therapeutics from bench to bedside:
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