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In this study, PEGylated GRg3-loaded niosomes were developed and characterized for potential AD treatment. Their efficacy was assessed using\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    models, as well as molecular dynamics simulations of self-assembly. Our formulation achieved a relatively high encapsulation efficiency of 83.02% and a controlled release profile, with 75.73% of the drug released over 48\u00a0h.\n                    <jats:italic>In vitro<\/jats:italic>\n                    , co-administration of A\u03b2 with free or PEGylated GRg3-loaded niosomes markedly reduced the levels of Total Antioxidant Capacity, Malondialdehyde (MDA), and\n                    <jats:italic>caspase-3<\/jats:italic>\n                    gene expression compared to the A\u03b2-only group.\n                    <jats:italic>In vivo<\/jats:italic>\n                    evaluations revealed that treatment with the niosomal formulation did not significantly alter behavioral parameters, MDA levels, or Superoxide Dismutase activity. However, catalase activity was significantly higher than in the control group. Histopathological and immunohistochemical analyses showed reduced neurovascular damage and preservation of blood\u2013brain barrier (BBB) and hippocampal integrity in the treated group. MD simulations confirmed the spontaneous self-assembly of surfactant molecules into a bilayer structure with successful incorporation of GRg3. Our findings underscore the potential of PEGylated niosomes as efficient nanocarriers for GRg3 delivery in the AD treatment.\n                  <\/jats:p>","DOI":"10.1038\/s41598-025-32528-3","type":"journal-article","created":{"date-parts":[[2025,12,14]],"date-time":"2025-12-14T16:13:44Z","timestamp":1765728824000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Ginsenoside Rg3-encapsulated pegylated niosomes exhibit multimodal therapeutic potential in Alzheimer\u2019s disease"],"prefix":"10.1038","volume":"16","author":[{"given":"Mahmood","family":"Barani","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farshid","family":"Zargari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shekoufeh","family":"Mirinejad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatemeh","family":"Madani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad Reza","family":"Hajinezhad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saman","family":"Sargazi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,12,14]]},"reference":[{"key":"32528_CR1","doi-asserted-by":"publisher","first-page":"1169","DOI":"10.12688\/f1000research.19775.1","volume":"8","author":"N Contreras-Puentes","year":"2019","unstructured":"Contreras-Puentes, N., Mercado-Camargo, J. & Alv\u00edz-Amador, A. 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