{
  "abstract": "Background/Objectives: Teriflunomide (TF) is a fluorinated oral therapy approved for relapsing-remitting multiple sclerosis that can be detected using fluorine-19 (¹⁹F) magnetic resonance (MR) methods. In preclinical studies, palatable drug delivery vehicles may facilitate voluntary oral administration and reduce procedure-related stress; however, they may also interact with the drug and alter its pharmacological and MR properties. We investigated whether sweetened milk (SM), compared with sucrose-containing carboxymethylcellulose (SCMC), affects the therapeutic efficacy, tissue distribution, and ¹⁹F MR signal of TF in experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. Methods: Twenty-four female SJL/J mice received TF (30 mg/kg/day) in SM or SCMC, or the corresponding vehicle controls, by micropipette-guided drug administration (MDA) from day -2 to day 22. Clinical disease was monitored; hepatic TF was assessed ex vivo by ¹⁹F MR spectroscopy (MRS) and imaging (MRI) at 9.4 T; and brain TF was quantified by HPLC-MS. Formulation-dependent ¹⁹F MR spectral and MR relaxation properties were examined in vitro using phantoms containing TF in different vehicles, including DMSO, SM, SCMC, and serum. Intrinsic pharmacodynamic activity was evaluated by dihydroorotate dehydrogenase (DHODH) inhibition. Results: TF in SCMC reduced EAE severity during peak disease and delayed disease onset, whereas TF in SM produced no sustained therapeutic benefit. Hepatic ¹⁹F MR signals were approximately twofold higher with SCMC than with SM, and brain TF concentrations were 4.8-fold higher. Phantom studies revealed formulation-dependent changes in chemical shift, spectral linewidth, and the MRI relaxation time T₂, including a 65-fold shortening in CMC + SM relative to CMC alone. SM did not reduce the intrinsic DHODH inhibitory potency of TF, indicating that the diminished in vivo efficacy was not attributable to impaired pharmacodynamic activity. Conclusions: As an oral delivery vehicle, sweetened milk altered TF therapeutic efficacy, as well as ¹⁹F MR signal and tissue distribution in the EAE model. Palatable vehicles used for voluntary oral treatment should therefore be carefully selected and validated, as vehicle-drug interactions may alter tissue exposure, confound ¹⁹F MR detection and, more importantly, compromise therapeutic efficacy.",
  "abstract_shown": true,
  "affiliations": [
    "Berlin Ultrahigh Field Facility, Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association (MDC), 13125 Berlin, Germany.",
    "Charité-Universitätsmedizin Berlin, 10117 Berlin, Germany.",
    "Experimental and Clinical Research Center (ECRC), A Joint Cooperation Between the Charité Medical Faculty and the Max-Delbrück Center for Molecular Medicine in the Helmholtz Association, 13125 Berlin, Germany.",
    "Medicinal Chemistry, Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), 13125 Berlin, Germany.",
    "SRH Fernhochschule-The Mobile University, 88499 Riedlingen, Germany.",
    "Tool Time GmbH, 10245 Berlin, Germany.",
    "Lipidomix GmbH, 13125 Berlin, Germany."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 15,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Xiang Hu",
      "orcid": "0009-0007-6992-3056"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Nandita Saha",
      "orcid": "0000-0001-8555-2477"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Yinhao Chen",
      "orcid": "0009-0005-0789-745X"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Jason M Millward",
      "orcid": "0000-0003-4484-2798"
    },
    {
      "affs": [
        3
      ],
      "name": "Andreas Oder"
    },
    {
      "affs": [
        3
      ],
      "name": "Keven Mallow"
    },
    {
      "affs": [
        0
      ],
      "name": "Stefanie Münchberg"
    },
    {
      "affs": [
        4
      ],
      "name": "Christian Prinz",
      "orcid": "0000-0003-3330-031X"
    },
    {
      "affs": [
        5
      ],
      "name": "Helmar Waiczies",
      "orcid": "0000-0001-6651-4790"
    },
    {
      "affs": [
        6
      ],
      "name": "Michael Rothe"
    },
    {
      "affs": [
        3
      ],
      "name": "Martin Neuenschwander",
      "orcid": "0000-0002-3114-7975"
    },
    {
      "affs": [
        3
      ],
      "name": "Marc Nazaré",
      "orcid": "0000-0002-1602-2330"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Friedemann Paul"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Thoralf Niendorf",
      "orcid": "0000-0001-7584-6527"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Sonia Waiczies",
      "orcid": "0000-0002-9916-9572"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/2r5b922gf2tzm.bib",
  "cited_by": 0,
  "doi": "10.3390/pharmaceutics18101225",
  "fulltext_url": "https://europepmc.org/articles/PMC13708660",
  "id": "2r5b922gf2tzm",
  "issns": [
    "1999-4923"
  ],
  "landing_url": "https://europepmc.org/article/MED/42942759",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2734|Multiple Sclerosis Research Studies"
    ]
  ],
  "openalex": "W7214666545",
  "pdf_url": "https://europepmc.org/articles/PMC13708660?pdf=render",
  "pmcid": "PMC13708660",
  "pmid": "42942759",
  "published": "2026-09-27",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/2r5b922gf2tzm.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:22:24Z",
      "native_id": "MED:42942759",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42942759"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2734|Multiple Sclerosis Research Studies",
      "subfield": "general"
    }
  ],
  "title": "Drug Delivery Vehicle-Teriflunomide Interactions Affect Treatment and Fluorine Magnetic Resonance in an Animal Model of Multiple Sclerosis.",
  "title_text": "Drug Delivery Vehicle-Teriflunomide Interactions Affect Treatment and Fluorine Magnetic Resonance in an Animal Model of Multiple Sclerosis.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:22:24Z",
  "url": "https://research.draconitic.com/paper/2r5b922gf2tzm",
  "venue": "Pharmaceutics",
  "versions": []
}