{
  "abstract": "Donepezil, a reversible acetylcholinesterase inhibitor, is widely used for the symptomatic treatment of Alzheimer’s disease (AD). Although higher-dose donepezil has been shown to provide additional clinical benefit, dose escalation is often limited by cholinergic adverse effects. Given that approximately 96% of circulating donepezil is bound to plasma proteins, especially albumin, we hypothesized that increasing its unbound fraction from albumin may improve brain delivery without increasing the administered dose. To achieve this goal, herein we examined whether the donepezil-albumin complex can be dissociated by low-intensity focused ultrasound (FUS) in vitro. Then brain uptake of donepezil was evaluated in mice receiving intravenous donepezil followed by targeted brain FUS stimulation. As a result, FUS significantly increased unbound fraction of donepezil at the targeted region in vitro, resulting in a 41.1% increase of donepezil diffusion into dialysis cassettes compared with non-sonicated controls. In mice receiving intravenous donepezil, targeted brain FUS stimulation increased brain donepezil concentrations by 52.7% at 15-min post-administration time. These findings suggest that low-intensity FUS enhances brain uptake of donepezil, potentially through modulation of donepezil-albumin binding, and support further investigation of plasma protein binding-targeted brain drug delivery.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Pharmacy, Yonsei University, Incheon 21983 Chuncheon 24252 Korea",
    "Bionics Research Center, Biomedical Research Division, Korea Institute of Science and Technology, Seoul 02792 Chuncheon 24252 Korea",
    "Advanced Analysis and Data Center, Korea Institute of Science and Technology, Seoul 02792 Chuncheon 24252 Korea",
    "School of Mathematics and Computing (Computational Science and Engineering), Yonsei University, Seoul 03722 Chuncheon 24252 Korea",
    "Department of Neurology, Dongtan Sacred Heart Hospital, Hallym University College of Medicine, Hwaseong 18450 Chuncheon 24252 Korea",
    "Research Institute for Complementary and Alternative Medicine, Hallym University Chuncheon 24252 Korea"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Songmin Lee"
    },
    {
      "affs": [
        0
      ],
      "name": "Kyeonghwan Kim"
    },
    {
      "affs": [
        1
      ],
      "name": "Hyungmin Kim"
    },
    {
      "affs": [
        2
      ],
      "name": "Min-Seok Oh"
    },
    {
      "affs": [
        3
      ],
      "name": "Kyungho Yoon"
    },
    {
      "affs": [
        0
      ],
      "name": "Subin Kwak"
    },
    {
      "affs": [
        0
      ],
      "name": "JiMin Kim"
    },
    {
      "affs": [
        2
      ],
      "name": "Gwan-Ho Lee"
    },
    {
      "affs": [
        0
      ],
      "name": "YoungSoo Kim"
    },
    {
      "affs": [
        4,
        5
      ],
      "name": "Jaeho Kim"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/2cntkhc0s9496.bib",
  "cited_by": 0,
  "doi": "10.5607/en26028",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13728862/",
  "id": "2cntkhc0s9496",
  "issns": [
    "1226-2560",
    "2093-8144"
  ],
  "landing_url": "https://doi.org/10.5607/en26028",
  "language": "en",
  "licence": "CC-BY-NC-4.0",
  "licence_label": "CC BY-NC 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Original Article"
    ],
    [
      "openalex",
      "2204|Ultrasound and Hyperthermia Applications"
    ]
  ],
  "openalex": "W7222552364",
  "pdf_url": "https://www.en-journal.org/journal/download_pdf.php?uid=724",
  "pmcid": "PMC13728862",
  "pmid": "42885191",
  "published": "2026-10-31",
  "publisher": "Korean Society for Brain and Neural Science",
  "ris": "https://research.draconitic.com/paper/2cntkhc0s9496.ris",
  "sources": [
    {
      "first_seen": "2026-11-07T12:21:44Z",
      "native_id": "PMC13728862",
      "source": "pmc",
      "url": "https://doi.org/10.5607/en26028"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "journal-openalex:F28",
      "subfield": "neuroscience"
    }
  ],
  "title": "Focused Ultrasound as a Plasma Protein Binding-targeted Strategy to Enhance Brain Uptake of Donepezil",
  "title_text": "Focused Ultrasound as a Plasma Protein Binding-targeted Strategy to Enhance Brain Uptake of Donepezil",
  "type": "peer-reviewed",
  "updated_at": "2026-11-07T12:21:44Z",
  "url": "https://research.draconitic.com/paper/2cntkhc0s9496",
  "venue": "Experimental Neurobiology",
  "versions": []
}