{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T15:49:12Z","timestamp":1790092152790,"version":"4.0.1"},"reference-count":148,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T00:00:00Z","timestamp":1784073600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Bioeng. Biotechnol."],"abstract":"<jats:p>The complex and heterogeneous physiological barriers of the gastrointestinal (GI) tract severely limit the efficacy of therapeutic agents for local diseases. This review comprehensively examines strategies for translating targeted drug delivery \u201cfrom bench to bowel\u201d within the GI tract. We detail the unique biological barriers across GI segments (oral cavity, esophagus, stomach, small intestine, colon) and analyze core challenges in designing effective delivery systems: payload stability, precise targeting\/retention, controlled release, mucosal\/epithelial penetration, and biocompatibility. The article critically evaluates recent advancements in key delivery platforms, including nanocarriers (liposomes, polymeric NPs, dendrimers, inorganic NPs), hydrogels, and microscale systems (microspheres, microneedles, microrobots), categorizing them by their targeting mechanisms: passive (e.g., the classical EPR effect in solid tumors and EPR-like permeability\/retention phenomena in inflamed GI lesions), passive (e.g., EPR effect), active (ligand-mediated), and stimuli-responsive (pH, enzymes, redox, etc.). Furthermore, we highlight the transformative applications of these targeted systems in treating major GI diseases such as inflammatory bowel disease (IBD), GI cancers, and peptic ulcer disease, emphasizing their potential to enhance local efficacy while minimizing systemic toxicity. This work bridges fundamental principles with translational progress to provide a roadmap for developing clinically viable targeted therapies for GI diseases.<\/jats:p>","DOI":"10.3389\/fbioe.2026.1763085","type":"journal-article","created":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T06:05:15Z","timestamp":1784095515000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["From bench to bowel: translating targeted drug delivery through gastrointestinal barriers"],"prefix":"10.3389","volume":"14","author":[{"given":"Zhou","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Endoscopy Center, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenxin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery the Second Affiliated Hospital, Zhejiang University School of Medicine","place":["Hangzhou, China"]},{"name":"Orthopedics Research Institute of Zhejiang University","place":["Hangzhou, China"]},{"name":"Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province","place":["Hangzhou, China"]},{"name":"Clinical Research Center of Motor System Disease of Zhejiang Province","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinhao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery the Second Affiliated Hospital, Zhejiang University School of Medicine","place":["Hangzhou, China"]},{"name":"Orthopedics Research Institute of Zhejiang University","place":["Hangzhou, China"]},{"name":"Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province","place":["Hangzhou, China"]},{"name":"Clinical Research Center of Motor System Disease of Zhejiang Province","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangqian","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery the Second Affiliated Hospital, Zhejiang University School of Medicine","place":["Hangzhou, China"]},{"name":"Orthopedics Research Institute of Zhejiang University","place":["Hangzhou, China"]},{"name":"Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province","place":["Hangzhou, China"]},{"name":"Clinical Research Center of Motor System Disease of Zhejiang Province","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohua","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery the Second Affiliated Hospital, Zhejiang University School of Medicine","place":["Hangzhou, China"]},{"name":"Orthopedics Research Institute of Zhejiang University","place":["Hangzhou, China"]},{"name":"Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province","place":["Hangzhou, China"]},{"name":"Clinical Research Center of Motor System Disease of Zhejiang Province","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liangliang","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Endoscopy Center, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,15]]},"reference":[{"key":"B1","unstructured":"Advancements in colon-targeted drug delivery: a comprehensive review on recent techniques with emphasis on hot-melt extrusion and 3D printing technologies - PubMed\n          \n          39379609\n          \n          2025"},{"key":"B2","doi-asserted-by":"publisher","first-page":"7191","DOI":"10.2147\/IJN.S213836","article-title":"In vitro-in vivo evaluation of chitosan-PLGA nanoparticles for potentiated gastric retention and anti-ulcer activity of diosmin","volume":"14","author":"Abd El Hady","year":"2019","journal-title":"Int. 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