{
  "abstract": "A drug-drug cocrystal strategy harnessing natural product synergy was developed to address the oral delivery barriers of breviscapine (BRE), a natural flavonoid with poor solubility and extensive first-pass metabolism. BRE was integrated with the monoterpenoid permeation enhancer borneol (BO) via solvent evaporation to form a stable supramolecular assembly. Comprehensive solid-state characterization and density functional theory calculations confirmed that the cocrystal lattice is stabilized by specific hydrogen bonding between the flavonoid and terpenoid scaffolds. The optimized BRE-BO cocrystal exhibited highly synchronized release of both natural products (R² = 0.86), in contrast to the discordant dissolution of the physical mixture, with kinetics following the Korsmeyer-Peppas model (n = 0.45) indicative of Fickian diffusion. In vivo pharmacokinetic evaluation in rats demonstrated that the synergy conferred by co-delivered BO resulted in a 1.6-fold enhancement in oral bioavailability (AUC₀₋₂₄), a prolonged Tmax (from 2.3 to 3.3 h), and an elevated Cmax (1.2 vs. 0.8 mg/L) compared to bulk BRE. These findings demonstrate that drug-drug cocrystallization can simultaneously achieve dissolution synchronization and pharmacokinetic optimization, providing a viable strategy for the formulation of poorly bioavailable natural flavonoids without the use of polymeric excipients.",
  "abstract_shown": true,
  "affiliations": [
    "Yunnan Key Laboratory of Chinese Medicine Processing, College of Chinese Materia Medica, Yunnan University of Chinese Medicine, Kunming, 650500, China.",
    "General Hospital of Ningxia Medical University, Yinchuan, 750004, China. mayanni2005@163.com.",
    "Yunnan Key Laboratory of Chinese Medicine Processing, College of Chinese Materia Medica, Yunnan University of Chinese Medicine, Kunming, 650500, China. wangwenping@ynucm.edu.cn."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Jiao Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Caixian Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Yan Ma"
    },
    {
      "affs": [
        0
      ],
      "name": "Tong Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Anguo Hou"
    },
    {
      "affs": [
        0
      ],
      "name": "Wenbin Jin"
    },
    {
      "affs": [
        1
      ],
      "name": "Yanni Ma"
    },
    {
      "affs": [
        2
      ],
      "name": "Wenping Wang",
      "orcid": "0009-0009-6115-3880"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/a1a6hj828cpv0.bib",
  "cited_by": 0,
  "doi": "10.1007/s13659-026-00648-6",
  "fulltext_url": "https://europepmc.org/articles/PMC13728050",
  "id": "a1a6hj828cpv0",
  "issns": [
    "2192-2195",
    "2192-2209"
  ],
  "landing_url": "https://europepmc.org/article/MED/42970205",
  "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": [
    [
      "heading",
      "Original Article"
    ],
    [
      "openalex",
      "3003|Drug Solubulity and Delivery Systems"
    ]
  ],
  "openalex": "W7225120281",
  "pdf_url": "https://europepmc.org/articles/PMC13728050?pdf=render",
  "pmcid": "PMC13728050",
  "pmid": "42970205",
  "published": "2026-11-02",
  "publisher": "Springer",
  "ris": "https://research.draconitic.com/paper/a1a6hj828cpv0.ris",
  "sources": [
    {
      "first_seen": "2026-11-04T15:20:43Z",
      "native_id": "MED:42970205",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42970205"
    },
    {
      "first_seen": "2026-11-06T12:23:48Z",
      "native_id": "PMC13728050",
      "source": "pmc",
      "url": "https://doi.org/10.1007/s13659-026-00648-6"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:3003|Drug Solubulity and Delivery Systems",
      "subfield": "pharmacology-toxicology"
    }
  ],
  "title": "A drug-drug cocrystal of breviscapine and borneol: harnessing natural product synergy for synchronized release and improved pharmacokinetics.",
  "title_text": "A drug-drug cocrystal of breviscapine and borneol: harnessing natural product synergy for synchronized release and improved pharmacokinetics.",
  "type": "peer-reviewed",
  "updated_at": "2026-11-07T12:21:06Z",
  "url": "https://research.draconitic.com/paper/a1a6hj828cpv0",
  "venue": "Natural products and bioprospecting",
  "versions": []
}