ArticleInternational journal of biological macromolecules2026
Multi-functionalized chitosan-Extracellular vesicles nanohybrid system for intranasal delivery of pApoE2 to attenuate age-related inflammation.
Article in International journal of biological macromolecules, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Neuroinflammation in aging is a chronic, low-grade inflammatory state in the brain that worsens with age and is linked to neurodegeneration. It is characterized by elevated pro-inflammatory cytokines, oxidative stress, impaired microglial function, activated glia, and astrocytes. Higher ApoE2 expression in the brain attenuates neuroinflammation. The nano-hybrid-mediated approach was employed for effective intranasal (IN) delivery of a plasmid encoding ApoE2 (pApoE2) to investigate its effect on age-related neuroinflammation. The nanohybrid demonstrated enhanced pDNA loading (89.1%) compared to extracellular vesicles (EVs) (10.4%), was <230 nm in size, and was non-toxic to brain cells. The nanohybrid/pApoE2 complex demonstrated significantly higher (p ≤ 0.05) cellular transfection efficiency in primary astrocytes and neurons than EVs (12.3 ± 3.8 and 10.5 ± 1.5 ng/mg of protein, respectively). In vivo brain transfection via nanohybrid/pApoE2 showed significantly higher (p ≤ 0.05) ApoE expression across all treated groups, at 57.7 ± 13.8 ng/mg of protein. Comparative analysis of pro-inflammatory cytokines in 3-month-old and 24-month-old mice revealed higher neuroinflammation in the older mice. The nanohybrid/pApoE2 complex-treated mice have shown a significant reduction in the TNF-α, IL-6, and IL-1β expression in the brain, plasma, and spleen. Our study elucidates a therapeutic approach of nanohybrid-mediated IN administration of pApoE2 against inflammaging.
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