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Patchouli alcohol (PA) has demonstrated effectiveness in treating gastric ulcers through antioxidative and anti\u2010inflammatory effects. However, the water insolubility of PA and rapid gastric emptying cause low drug concentration and poor absorption in the stomach, resulting in limited treatment efficacy of PA. This study develops an oral gastroretentive raft forming system (GRFDDS) containing the aminated hollow mesoporous silica nanoparticles (NH<jats:sub>2<\/jats:sub>\u2010HMSN) for PA delivery. The application of NH<jats:sub>2<\/jats:sub>\u2010HMSN can enhance PA\u2010loading capacity and water dispersibility, promoting bio\u2010adhesion to the gastric mucosa and sustained drug release. The incorporation of PA\u2010loaded NH<jats:sub>2<\/jats:sub>\u2010HMSN (NH<jats:sub>2<\/jats:sub>\u2010HMSN\u2010PA) into GRFDDS can facilitate gastric drug retention and achieve long action, thereby improving therapeutic effects. The results reveal that NH<jats:sub>2<\/jats:sub>\u2010HMSN\u2010PA protects the gastric mucosa damage by inhibiting NLRP3\u2010mediated pyroptosis. The GRFDDS, optimized through orthogonal design, demonstrates the gastric retention capacity and sustained drug release, exhibiting significant therapy efficacy in an ethanol\u2010induced acute gastric ulcers\u00a0model and an aspirin\u2010induced chronic gastric ulcers\u00a0model through antioxidation, anti\u2010pyroptosis, and anti\u2010inflammation. This study provides a potential strategy for enhancing druggability of insoluble natural compounds and therapeutic management of gastric ulcers.<\/jats:p>","DOI":"10.1002\/adhm.202400566","type":"journal-article","created":{"date-parts":[[2024,5,20]],"date-time":"2024-05-20T06:40:34Z","timestamp":1716187234000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Gastroretentive Raft Forming System for Enhancing Therapeutic Effect of Drug\u2010Loaded Hollow Mesoporous Silica on Gastric Ulcers"],"prefix":"10.1002","volume":"13","author":[{"given":"Huayuan","family":"Chen","sequence":"first","affiliation":[{"name":"School of Pharmaceutical Sciences Southern Medical University  Guangzhou 510515 China"},{"name":"Zhongshan Institute for Drug Discovery Shanghai Institute of Materia Medica Chinese Academy of Sciences  Zhongshan 528400 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Pan","sequence":"additional","affiliation":[{"name":"School of Pharmacy Zunyi Medical University  Zunyi 563003 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengyu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Artemisinin Research Center Guangzhou University of Chinese Medicine  12 Jichang Road Guangzhou 510450 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences Southern Medical University  Guangzhou 510515 China"},{"name":"Zhongshan Institute for Drug Discovery Shanghai Institute of Materia Medica Chinese Academy of Sciences  Zhongshan 528400 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Tu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Drug Research Shanghai Institute of Materia Medica Chinese Academy of Sciences  Shanghai 201203 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ergang","family":"Liu","sequence":"additional","affiliation":[{"name":"Zhongshan Institute for Drug Discovery Shanghai Institute of Materia Medica Chinese Academy of Sciences  Zhongshan 528400 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7067-8915","authenticated-orcid":false,"given":"Yongzhuo","family":"Huang","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences Southern Medical University  Guangzhou 510515 China"},{"name":"Zhongshan Institute for Drug Discovery Shanghai Institute of Materia Medica Chinese Academy of Sciences  Zhongshan 528400 China"},{"name":"Artemisinin Research Center Guangzhou University of Chinese Medicine  12 Jichang Road Guangzhou 510450 China"},{"name":"State Key Laboratory of Drug Research Shanghai Institute of Materia Medica Chinese Academy of Sciences  Shanghai 201203 China"},{"name":"NMPA Key Laboratory for Quality Research and Evaluation of Pharmaceutical Excipients  Shanghai 201203 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,5,20]]},"reference":[{"key":"e_1_2_10_1_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2008.00677.x"},{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)31678-6"},{"key":"e_1_2_10_3_1","first-page":"861","volume":"76","author":"Collatuzzo G.","year":"2022","journal-title":"Br. 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