Neuroprotective Effects of Intranasally Delivered Exosomes Doped with Curcumin in a Murine Model of Alzheimer’s Disease

International Journal of Medical Advances and Discoveries | Vol. 16, No. 10, October 2025 | pp. 68–76

DOI: 10.46882/2025/IJMAD/000109

Original Research Article

Title: Neuroprotective Effects of Intranasally Delivered Exosomes Doped with Curcumin in a Murine Model of Alzheimer’s Disease

Names of Authors: Yukihiro Tanaka¹, Alia M. Al-Shami², Richard P. Gallagher¹

Authors’ Affiliations: ¹Department of Neurosciences, Kyoto University Graduate School of Medicine, Kyoto, Japan; ²Department of Pharmaceutics, American University of Beirut, Beirut, Lebanon

Abstract: Efficient drug delivery across the blood-brain barrier (BBB) presents a critical hurdle in therapeutic drug development for Alzheimer’s disease (AD). This study investigated the neuroprotective, anti-inflammatory, and amyloid-clearing capabilities of mesenchymal stem cell-derived exosomes engineered to encapsulate curcumin (Exo-Cur) administered via a non-invasive intranasal pathway. Transgenic APP/PS1 mice (age: 6 months, n = 80) were treated intranasally with Exo-Cur (5 mg/kg), free curcumin, empty exosomes, or a vehicle control daily for 8 consecutive weeks. Spatial learning and memory evaluations via the Morris Water Maze demonstrated that Exo-Cur treated mice had significantly shorter escape latencies (22.4 ± 3.1 seconds) compared to the free curcumin (41.2 ± 4.5 seconds) and vehicle cohorts (55.8 ± 5.2 seconds; p < 0.001). Immunohistochemical analysis revealed a 48% reduction in cortical and hippocampal beta-amyloid (A-beta) plaque burden within the Exo-Cur group (p < 0.001). Enzyme-linked immunosorbent assays (ELISA) demonstrated a profound attenuation of pro-inflammatory cytokines, specifically IL-1-beta (-56%) and TNF-alpha (-62%), alongside a marked reduction in microglial activation (Iba1 immunoreactivity, p = 0.002). Western blot tracking confirmed the up-regulation of brain-derived neurotrophic factor (BDNF) and postsynaptic density protein-95 (PSD-95) in treated brain tissues. Intranasal delivery of Exo-Cur effectively bypasses the BBB, producing substantial anti-amyloid and anti-inflammatory neuroprotective benefits in AD models.

Keywords: Exosomes, Curcumin, Alzheimer’s disease, Blood-brain barrier, Intranasal delivery, Neuroinflammation

Manuscript Timeline: Received: July 11, 2025; Revised: August 20, 2025; Accepted: September 10, 2025; Published: October 24, 2025

Citation: Tanaka, Y., Al-Shami, M. A., & Gallagher, P. R. (2025). Neuroprotective Effects of Intranasally Delivered Exosomes Doped with Curcumin in a Murine Model of Alzheimer’s Disease. International Journal of Medical Advances and Discoveries, 16(10), 68–76. doi.org

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