{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T05:02:19Z","timestamp":1787461339921,"version":"build-2736575974"},"reference-count":43,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,4,12]],"date-time":"2025-04-12T00:00:00Z","timestamp":1744416000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2021YFC2103100"],"award-info":[{"award-number":["2021YFC2103100"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Wuxi Taihu Lake Talent Plan","award":["2021YFC2103100"],"award-info":[{"award-number":["2021YFC2103100"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background: Ulcerative colitis (UC), a subtype of chronic inflammatory bowel disease (IBD), is primarily treated with oral medications to reduce inflammation and alleviate symptoms. Celecoxib (CXB) is an attractive candidate for UC; however, its limited solubility and low bioavailability pose significant challenges to its clinical application. Methods: We reported a novel chondroitin sulfate A\u2013Celecoxib (CSA-CXB) polymeric nanoprodrug to address the limited solubility and low bioavailability of CXB. CXB was conjugated to chondroitin sulfate A (CSA) via succinic anhydride (SA) and ethylenediamine to prepare CSA-CXB polymers, which can self-assemble into nanoparticle structural prodrugs in aqueous condition. We investigated the stability, blood compatibility, and responsiveness of the nanoparticles. The ability of the nanoparticles to treat UC in vitro and in vivo was then evaluated. Results: The CSA-CXB nanoprodrug was spherical with a mean particle size of 188.4 \u00b1 2.2 nm, a zeta potential of \u221222.9 \u00b1 0.1 mV, and sustained drug release behavior. Furthermore, CSA-CXB exhibited remarkable antioxidant and anti-inflammatory effects, as it can significantly increase the free radical scavenging rate and reduce the expression level of ROS, TNF-\u03b1, IL-6, nitric oxide (NO), and COX-2 protein in vitro. In vivo results demonstrated that CSA-CXB targeted the mice\u2019s colon efficiently mitigate UC symptoms by inhibiting the expression of inflammatory cytokine. Conclusions: The CSA-CXB nanoprodrug can improve the therapeutic impact of CXB, and has potential as a new preparation for a clinical UC treatment nanoprodrug.<\/jats:p>","DOI":"10.3390\/pharmaceutics17040511","type":"journal-article","created":{"date-parts":[[2025,4,14]],"date-time":"2025-04-14T07:42:01Z","timestamp":1744616521000},"page":"511","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Amphiphilic Celecoxib-Polysaccharide Delivery System for Enhanced Colon-Targeted Colitis Therapy"],"prefix":"10.3390","volume":"17","author":[{"given":"Qiao","family":"Qiao","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, Affiliated Hospital of Jiangnan University, Wuxi 214122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xian","family":"Wan","sequence":"additional","affiliation":[{"name":"School of Life Sciences and Health Engineering, Jiangnan University, Wuxi 214122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Li","sequence":"additional","affiliation":[{"name":"School of Life Sciences and Health Engineering, Jiangnan University, Wuxi 214122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weijun","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Life Sciences and Health Engineering, Jiangnan University, Wuxi 214122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enxuan","family":"Li","sequence":"additional","affiliation":[{"name":"The Second Clinical Medical School, Nanjing Medical University, Nanjing 210029, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7546-7420","authenticated-orcid":false,"given":"Lipeng","family":"Qiu","sequence":"additional","affiliation":[{"name":"School of Life Sciences and Health Engineering, Jiangnan University, Wuxi 214122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiming","family":"Tu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Affiliated Hospital of Jiangnan University, Wuxi 214122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1016\/S0140-6736(23)00966-2","article-title":"Ulcerative Colitis","volume":"402","author":"Honap","year":"2023","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e37095","DOI":"10.1097\/MD.0000000000037095","article-title":"Global Trends and Hotspots of Ulcerative Colitis Based on Bibliometric and Visual Analysis from 1993 to 2022","volume":"103","author":"Wang","year":"2023","journal-title":"Medicine"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2211846","DOI":"10.1002\/adfm.202211846","article-title":"Surface-Engineered Vanadium Carbide MXenzyme for Anti-Inflammation and Photoenhanced Antitumor Therapy of Colon Diseases","volume":"33","author":"Deng","year":"2023","journal-title":"Adv. Funct. Mater."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1016\/j.cell.2010.01.025","article-title":"Immunity, Inflammation, and Cancer","volume":"140","author":"Grivennikov","year":"2010","journal-title":"Cell"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Zhang, M., Li, X., Zhang, Q., Yang, J., and Liu, G. (2023). Roles of Macrophages on Ulcerative Colitis and Colitis-Associated Colorectal Cancer. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1103617"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"294","DOI":"10.12688\/f1000research.20805.1","article-title":"Ulcerative Colitis: Recent Advances in the Understanding of Disease Pathogenesis","volume":"9","author":"Porter","year":"2020","journal-title":"F1000Research"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1023\/A:1018849405922","article-title":"Increased Nitric Oxide Production and Inducible Nitric Oxide Synthase Activity in Colonic Mucosa of Patients with Active Ulcerative Colitis and Crohn\u2019s Disease","volume":"42","author":"Kimura","year":"1997","journal-title":"Dig. Dis. Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"100851","DOI":"10.1016\/j.disamonth.2019.02.004","article-title":"A Comprehensive Review and Update on Ulcerative Colitis","volume":"65","author":"Gajendran","year":"2019","journal-title":"Dis.-A-Mon."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"175628482211381","DOI":"10.1177\/17562848221138160","article-title":"A Review of the Therapeutic Management of Ulcerative Colitis","volume":"15","author":"Aslam","year":"2022","journal-title":"Ther. Adv. Gastroenterol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2457","DOI":"10.2165\/11208240-000000000-00000","article-title":"Celecoxib: A Review of Its Use for Symptomatic Relief in the Treatment of Osteoarthritis, Rheumatoid Arthritis and Ankylosing Spondylitis","volume":"71","author":"McCormack","year":"2011","journal-title":"Drugs"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1663","DOI":"10.1038\/s41385-018-0018-3","article-title":"Colonic Epithelial mTORC1 Promotes Ulcerative Colitis through COX-2-Mediated Th17 Responses","volume":"11","author":"Lin","year":"2018","journal-title":"Mucosal Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1080\/08923973.2023.2300508","article-title":"Celecoxib Alleviates the DSS-Induced Ulcerative Colitis in Mice by Enhancing Intestinal Barrier Function, Inhibiting Ferroptosis and Suppressing Apoptosis","volume":"46","author":"Li","year":"2024","journal-title":"Immunopharmacol. Immunotoxicol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1007\/s12272-013-0202-7","article-title":"In Situ Intestinal Permeability and in Vivo Oral Bioavailability of Celecoxib in Supersaturating Self-Emulsifying Drug Delivery System","volume":"37","author":"Song","year":"2014","journal-title":"Arch. Pharm. Res."},{"key":"ref_14","first-page":"108","article-title":"Celecoxib-Induced Acute Generalized Exanthematous Pustulosis: Uncommon and under-Recognized Side Effect","volume":"23","author":"Singh","year":"2024","journal-title":"EXCLI J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3028","DOI":"10.2174\/0929867328666210910125229","article-title":"The Role of Celecoxib as a Potential Inhibitor in the Treatment ofInflammatory Diseases\u2014A Review","volume":"29","author":"Cruz","year":"2022","journal-title":"CMC"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.carbpol.2019.05.067","article-title":"Review of Polysaccharide Particle-Based Functional Drug Delivery","volume":"221","author":"Barclay","year":"2019","journal-title":"Carbohydr. Polym."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.jconrel.2023.08.019","article-title":"Polysaccharide-Based Tumor Microenvironment-Responsive Drug Delivery Systems for Cancer Therapy","volume":"362","author":"Wu","year":"2023","journal-title":"J. Control. Release"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2359","DOI":"10.1007\/s10924-021-02052-2","article-title":"Polysaccharides; Classification, Chemical Properties, and Future Perspective Applications in Fields of Pharmacology and Biological Medicine (A Review of Current Applications and Upcoming Potentialities)","volume":"29","author":"Mohammed","year":"2021","journal-title":"J. Polym. Environ."},{"key":"ref_19","first-page":"100067","article-title":"Recent Advances in Polysaccharides Based Biomaterials for Drug Delivery and Tissue Engineering Applications","volume":"2","author":"Sood","year":"2021","journal-title":"Carbohydr. Polym. Technol. Appl."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"118875","DOI":"10.1016\/j.carbpol.2021.118875","article-title":"Polysaccharide Peptide Conjugates: Chemistry, Properties and Applications","volume":"280","author":"Mohan","year":"2022","journal-title":"Carbohydr. Polym."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1186\/s11671-017-2324-1","article-title":"Anti-Tumor Study of Chondroitin Sulfate-Methotrexate Nanogels","volume":"12","author":"Wang","year":"2017","journal-title":"Nanoscale Res. Lett."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"S14","DOI":"10.1016\/j.joca.2008.06.008","article-title":"Anti-Inflammatory Activity of Chondroitin Sulfate","volume":"16","author":"Iovu","year":"2008","journal-title":"Osteoarthr. Cartil."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1451","DOI":"10.1111\/j.1582-4934.2009.00826.x","article-title":"Immunomodulatory and Anti-Inflammatory Effects of Chondroitin Sulphate","volume":"13","author":"Montell","year":"2009","journal-title":"J. Cell. Mol. Med."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Xie, Y., Xu, W., Jin, Z., and Zhao, K. (2023). Chondroitin Sulfate Functionalized Palmitic Acid and Cysteine Cografted-Quaternized Chitosan for CD44 and Gut Microbiota Dual-Targeted Delivery of Curcumin. Mater. Today Bio, 20.","DOI":"10.1016\/j.mtbio.2023.100617"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1016\/S0140-6736(95)91991-0","article-title":"Increased Expression of CD44v6 and CD44v3 in Ulcerative Colitis but Not Colonic Crohn\u2019s Disease","volume":"345","author":"Rosenberg","year":"1995","journal-title":"Lancet"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1111\/j.1365-2230.1997.tb01040.x","article-title":"Changes in CD44 Isoform Expression during Inflammatory Skin Disease","volume":"22","author":"Harris","year":"1997","journal-title":"Clin. Exp. Dermatol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Azimijou, N., Karimi-Soflou, R., and Karkhaneh, A. (2024). CD44 Targeted-Chondroitin Sulfate Nanoparticles: Fine-Tuning Hydrophobic Groups to Enhance in Vitro pH-Responsiveness and in Vivo Efficacy for Advanced Breast Cancer Treatment. Biomater. Adv., 158.","DOI":"10.1016\/j.bioadv.2024.213776"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Kesharwani, P., Chadar, R., Sheikh, A., Rizg, W.Y., and Safhi, A.Y. (2022). CD44-Targeted Nanocarrier for Cancer Therapy. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.800481"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"117103","DOI":"10.1016\/j.carbpol.2020.117103","article-title":"Drug Delivery Systems Based on CD44-Targeted Glycosaminoglycans for Cancer Therapy","volume":"251","author":"Li","year":"2021","journal-title":"Carbohydr. Polym."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"121255","DOI":"10.1016\/j.carbpol.2023.121255","article-title":"CD44 Targeting Nanodrug Based on Chondroitin Sulfate for Melanoma Therapy by Inducing Mitochondrial Apoptosis Pathways","volume":"320","author":"Li","year":"2023","journal-title":"Carbohydr. Polym."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.carbpol.2019.02.084","article-title":"Preparation, Characterisation and in Vitro and in Vivo Evaluation of CD44-Targeted Chondroitin Sulphate-Conjugated Doxorubicin PLGA Nanoparticles","volume":"213","author":"Liu","year":"2019","journal-title":"Carbohydr. Polym."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.addr.2020.07.010","article-title":"Advanced Nanomedicines for the Treatment of Inflammatory Diseases","volume":"157","author":"Brusini","year":"2020","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.jconrel.2011.12.014","article-title":"Drug Targeting Systems for Inflammatory Disease: One for All, All for One","volume":"161","author":"Crielaard","year":"2012","journal-title":"J. Control. Release"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2921","DOI":"10.2147\/DDDT.S461977","article-title":"Nanoparticle-Based Drug Delivery Systems for Inflammatory Bowel Disease Treatment","volume":"18","author":"Gao","year":"2024","journal-title":"DDDT"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1831","DOI":"10.1002\/jps.23082","article-title":"N-Succinylaspart-1-Yl Celecoxib Is a Potential Colon-Specific Prodrug of Celecoxib with Improved Therapeutic Properties","volume":"101","author":"Lee","year":"2012","journal-title":"J. Pharm. Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.jcis.2016.12.070","article-title":"Design, Preparation and Characterization of pH-Responsive Prodrug Micelles with Hydrolyzable Anhydride Linkages for Controlled Drug Delivery","volume":"492","author":"Seetharaman","year":"2017","journal-title":"J. Colloid Interface Sci."},{"key":"ref_37","unstructured":"Dr. Reddy\u2019s Laboratories Ltd (2011). Process for Preparation of Celecoxib Crystalline Form. (EP2363395)."},{"key":"ref_38","unstructured":"Ferro, L.J., and Miyake, P.S. (2009). Polymorphic Crystalline Forms of Celecoxib. (US7476744)."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.msec.2017.02.030","article-title":"Reduction-Sensitive Micelles Self-Assembled from Amphiphilic Chondroitin Sulfate A-Deoxycholic Acid Conjugate for Triggered Release of Doxorubicin","volume":"75","author":"Liu","year":"2017","journal-title":"Mater. Sci. Eng. C"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1016\/S0140-6736(94)92831-2","article-title":"Oxidants and Free Radicals in Inflammatory Bowel Disease","volume":"344","author":"Grisham","year":"1994","journal-title":"Lancet"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1016\/0140-6736(93)90211-X","article-title":"Increased Nitric Oxide Synthesis in Ulcerative Colitis","volume":"341","author":"Middleton","year":"1993","journal-title":"Lancet"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/S0016-5085(98)70196-9","article-title":"Cyclooxygenase 2 Is Induced in Colonic Epithelial Cells in Inflammatory Bowel Disease","volume":"115","author":"Singer","year":"1998","journal-title":"Gastroenterology"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1016\/j.neuroscience.2010.02.069","article-title":"Chondroitin Sulfate Inhibits Lipopolysaccharide-Induced Inflammation in Rat Astrocytes by Preventing Nuclear Factor Kappa B Activation","volume":"167","author":"Gorina","year":"2010","journal-title":"Neuroscience"}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/17\/4\/511\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:13:28Z","timestamp":1760030008000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/17\/4\/511"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,12]]},"references-count":43,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2025,4]]}},"alternative-id":["pharmaceutics17040511"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics17040511","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,12]]}}}