{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T06:59:06Z","timestamp":1761893946347,"version":"build-2065373602"},"reference-count":54,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T00:00:00Z","timestamp":1761696000000},"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":"crossref","award":["82260771"],"award-info":[{"award-number":["82260771"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Jiangxi University of Chinese Medicine Science and Technology Innovation Team Development Program","award":["CXTD22001"],"award-info":[{"award-number":["CXTD22001"]}]},{"name":"Long-Term Project of Innovative Leading Talents of the Jiangxi \u201cDouble Thousand Plan\u201d","award":["jxsq2023101090"],"award-info":[{"award-number":["jxsq2023101090"]}]},{"name":"Jiangxi Province Chinese Medicine Standardization Project","award":["2023A20"],"award-info":[{"award-number":["2023A20"]}]},{"name":"Jiangxi Province \u201cScience Technology + Chinese Medicine\u201d Joint Program Project","award":["2023KZI01008"],"award-info":[{"award-number":["2023KZI01008"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background: Anemoside B4 (AB4), the major bioactive saponin from Pulsatilla chinensis, exhibits anti-inflammatory, anti-tumor, anti-apoptotic, and analgesic properties. However, its clinical translation for ulcerative colitis (UC) is constrained by poor epithelial permeability and low oral bioavailability. Objective: This study\u2019s objective was to engineer and optimize thermosensitive rectal in situ gels (ISGs) of AB4, incorporating suitable absorption enhancers to improve mucosal permeation, bioavailability, and therapeutic efficacy against UC. Methods: Screening of effective permeation enhancers was conducted using Caco-2 cell monolayers and Franz diffusion cells. Critical formulation variables such as poloxamer 407 (P407), poloxamer 188 (P188), and hydroxypropyl methyl cellulose (HPMC) were optimized, employing single-factor experiments coupled with the Box\u2013Behnken design response surface methodology (BBD-RSM). Comprehensive characterization encompassed in vitro release kinetics, in vivo pharmacokinetics, rectal tissue tolerability, rectal retention time, and pharmacodynamic efficacy in a UC model. Results: We used 2.5% hydroxypropyl-\u03b2-cyclodextrin (HP-\u03b2-CD) and 1.0% sodium caprate (SC) as the appropriate absorption enhancers, and the amounts of P407, P188, and HPMC were 17.41%, 4.07%, and 0.44%, respectively, to yield the corresponding in situ gels HP-\u03b2-CD-AB4-ISG and SC-AB4-ISG. The gel characterization, such as gelation temperature, gelation time, pH, gelation strength, etc., was in accordance with requirements. The ISGs did not stimulate or damage rectal tissue and remained in the rectum for a prolonged period. More importantly, an improvement in bioavailability and alleviation of UC were noted. Conclusion: Absorption enhancer-assisted, poloxamer-based thermosensitive rectal ISGs provide a safe, convenient, and effective platform for targeted delivery of AB4 to the colorectum. This strategy addresses key limitations of oral dosing and warrants further clinical development for UC and related colorectal inflammatory diseases.<\/jats:p>","DOI":"10.3390\/pharmaceutics17111400","type":"journal-article","created":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T17:38:22Z","timestamp":1761759502000},"page":"1400","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Anemoside B4 Rectal Thermosensitive In Situ Gel to Treat Ulcerative Colitis by Overcoming Oral Bioavailability Barriers with Absorption Enhancer-Assisted Delivery"],"prefix":"10.3390","volume":"17","author":[{"given":"Xiaomeng","family":"Lei","sequence":"first","affiliation":[{"name":"National Engineering Research Center of Chinese Medicine Solid Preparation Manufacturing Technology, Jiangxi University of Chinese Medicine, Nanchang 330006, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Canjian","family":"Wang","sequence":"additional","affiliation":[{"name":"National Engineering Research Center of Chinese Medicine Solid Preparation Manufacturing Technology, Jiangxi University of Chinese Medicine, Nanchang 330006, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mingyan","family":"Xia","sequence":"additional","affiliation":[{"name":"National Engineering Research Center of Chinese Medicine Solid Preparation Manufacturing Technology, Jiangxi University of Chinese Medicine, Nanchang 330006, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guansheng","family":"Zhang","sequence":"additional","affiliation":[{"name":"National Engineering Research Center of Chinese Medicine Solid Preparation Manufacturing Technology, Jiangxi University of Chinese Medicine, Nanchang 330006, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tangxun","family":"Wang","sequence":"additional","affiliation":[{"name":"National Engineering Research Center of Chinese Medicine Solid Preparation Manufacturing Technology, Jiangxi University of Chinese Medicine, Nanchang 330006, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Chen","sequence":"additional","affiliation":[{"name":"National Engineering Research Center of Chinese Medicine Solid Preparation Manufacturing Technology, Jiangxi University of Chinese Medicine, Nanchang 330006, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yufang","family":"Huang","sequence":"additional","affiliation":[{"name":"National Engineering Research Center of Chinese Medicine Solid Preparation Manufacturing Technology, Jiangxi University of Chinese Medicine, Nanchang 330006, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tiantian","family":"Wang","sequence":"additional","affiliation":[{"name":"National Engineering Research Center of Chinese Medicine Solid Preparation Manufacturing Technology, Jiangxi University of Chinese Medicine, Nanchang 330006, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dongxun","family":"Li","sequence":"additional","affiliation":[{"name":"National Engineering Research Center of Chinese Medicine Solid Preparation Manufacturing Technology, Jiangxi University of Chinese Medicine, Nanchang 330006, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenliu","family":"Zhang","sequence":"additional","affiliation":[{"name":"National Engineering Research Center of Chinese Medicine Solid Preparation Manufacturing Technology, Jiangxi University of Chinese Medicine, Nanchang 330006, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guosong","family":"Zhang","sequence":"additional","affiliation":[{"name":"National Engineering Research Center of Chinese Medicine Solid Preparation Manufacturing Technology, Jiangxi University of Chinese Medicine, Nanchang 330006, China"},{"name":"School of Pharmacy, Jiangxi University of Chinese Medicine, Nanchang 330006, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"9458","DOI":"10.3748\/wjg.v20.i28.9458","article-title":"Epidemiology, demographic characteristics and prognostic predictors of ulcerative colitis","volume":"20","author":"Lyra","year":"2014","journal-title":"World J. 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