{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T12:12:55Z","timestamp":1789042375659,"version":"build-2803163510"},"reference-count":59,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T00:00:00Z","timestamp":1788998400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82174074"],"award-info":[{"award-number":["82174074"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["82174074"],"award-info":[{"award-number":["82174074"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Objectives: Herpetrione (HPE) is a bioactive lignan recognized for its hepatoprotective properties; however, it exhibits limited oral bioavailability. This study aimed to classify HPE within the framework of the biopharmaceutics classification system (BCS) and to develop a nanoparticle formulation. Methods: To this end, a comprehensive investigation was conducted, encompassing computer prediction analysis, equilibrium solubility measurements across the gastrointestinal pH range, Caco-2 bidirectional transportation, in situ single-pass intestinal perfusion (SPIP), and molecular docking with P-glycoprotein (P-gp). Results: In silico analyses suggested that HPE possesses low solubility and low permeability characteristics. Experimental assays revealed pH-dependent solubility and inherently low aqueous dissolution. Unlike the computer prediction results, Caco-2 studies revealed moderate permeability but a high efflux ratio, suggestive of possible P-gp substrate activity for HPE, a finding further supported by molecular docking simulations. Conversely, SPIP studies demonstrated that the effective permeability (Peff) of jejunal intestinal segments exceeded the high-permeability threshold, thereby classifying HPE as a high-permeability drug. Based on these findings, HPE was classified as a BCS class II compound. To overcome its solubility-limited absorption, a nanoparticle was developed, resulting in a marked enhancement of both solubility and dissolution rates. Conclusions: These findings underscore the importance of integrating experimental biopharmaceutical evaluations with computational tools when designing delivery systems for natural products.<\/jats:p>","DOI":"10.3390\/pharmaceutics18091142","type":"journal-article","created":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T11:38:39Z","timestamp":1789040319000},"page":"1142","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Biopharmaceutical Profiling of Herpetrione: A BCS II Properties and P-gp Substrate Guiding Nanoparticle Design"],"prefix":"10.3390","volume":"18","author":[{"given":"Fang","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Air Force Medical Center, PLA, Air Force Medical University, Beijing 100142, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"given":"Xiang","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Air Force Medical Center, PLA, Air Force Medical University, Beijing 100142, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"}]},{"given":"Yuwen","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Air Force Medical Center, PLA, Air Force Medical University, Beijing 100142, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Xinyu","family":"Zong","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Air Force Medical Center, PLA, Air Force Medical University, Beijing 100142, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Yazhong","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Air Force Medical Center, PLA, Air Force Medical University, Beijing 100142, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"conceptualization","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1688-5654","authenticated-orcid":false,"given":"Hailong","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Air Force Medical Center, PLA, Air Force Medical University, Beijing 100142, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"conceptualization","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jep.2018.09.033","article-title":"Hepatoprotection of Herpetospermum caudigerum Wall. against CCl4-induced liver fibrosis on rats","volume":"229","author":"Li","year":"2019","journal-title":"J. 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