{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T12:00:49Z","timestamp":1792929649562,"version":"4.5.0"},"reference-count":32,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,28]],"date-time":"2025-12-28T00:00:00Z","timestamp":1766880000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000780","name":"European Union","doi-asserted-by":"crossref","award":["HR-RS00148"],"award-info":[{"award-number":["HR-RS00148"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Gels"],"abstract":"<jats:p>In this study, dextran-based hydrogels were synthesized in dimethyl sulfoxide via free-radical polymerization with three structurally different crosslinking agents: divinyl benzene (DVB), diethylene glycol diacrylate (DEGDA), and 4,4\u2032-di(methacryloylamino)azobenzene (DMAAazoB). Their morphology, swelling ability, mechanical properties, and potential for controlled release of the model substance (uracil) were examined, with the results showing that the chemical structure and chain length of the crosslinking agents significantly influence the structural and functional properties of hydrogels. Hydrogels crosslinked with DMAAazoB showed the highest swelling ability at pH 3 and pH 6 (2552 and 1696%, respectively), associated with protonation effects and sponge-like morphology, while simultaneously showing the lowest mechanical strength (20 and 47 MPa). In vitro simulations of gastrointestinal digestion showed that uracil was not released in the gastric phase, while in the intestinal environment, the release was significant, especially in Dex-DMAAzoB hydrogels (88.52%). The absence of azoreductases in the simulated system indicates that the release of the drug in real conditions would likely be even more pronounced. The Dex-DAAazoB hydrogel exhibited a slight antibacterial effect, producing inhibition zones of 8 and 7 mm against Escherichia coli ATCC 8739 and Staphylococcus epidermidis ATCC 12228, respectively. In contrast, the remaining hydrogel formulations showed no detectable antibacterial activity toward either bacterial strain, indicating their microbiological inertness and supporting their suitability as carrier matrices for antitumor drug delivery in colorectal cancer therapy. The obtained results confirm that azo-crosslinked dextran hydrogels, with an optimized amount of crosslinking agent, are promising carriers for the targeted and controlled delivery of antitumor drugs to the colorectal region.<\/jats:p>","DOI":"10.3390\/gels12010025","type":"journal-article","created":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T00:50:42Z","timestamp":1766969442000},"page":"25","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Part II: The Influence of Crosslinking Agents on the Properties and Colon-Targeted Drug Delivery Efficacy of Dextran-Based Hydrogels"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9765-8882","authenticated-orcid":false,"given":"Tamara","family":"Erceg","sequence":"first","affiliation":[{"name":"Faculty of Technology Novi Sad, University of Novi Sad, Bulevar cara Lazara 1, 21000 Novi Sad, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6473-5282","authenticated-orcid":false,"given":"Milo\u0161","family":"Radosavljevi\u0107","sequence":"additional","affiliation":[{"name":"Faculty of Technology Novi Sad, University of Novi Sad, Bulevar cara Lazara 1, 21000 Novi Sad, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9278-9330","authenticated-orcid":false,"given":"Milorad","family":"Milji\u0107","sequence":"additional","affiliation":[{"name":"Institute of Food Technology in Novi Sad, University of Novi Sad, Bulevar cara Lazara 1, 21000 Novi Sad, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5621-1788","authenticated-orcid":false,"given":"Aleksandra","family":"Cvetanovi\u0107 Kljaki\u0107","sequence":"additional","affiliation":[{"name":"Faculty of Technology Novi Sad, University of Novi Sad, Bulevar cara Lazara 1, 21000 Novi Sad, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3828-8500","authenticated-orcid":false,"given":"Sebastian","family":"Balo\u0161","sequence":"additional","affiliation":[{"name":"Faculty of Technical Sciences, University of Novi Sad, Trg Dositeja Obradovi\u0107a 6, 21000 Novi Sad, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katarina Mi\u0161kovi\u0107","family":"\u0160poljari\u0107","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, Josipa Huttlera 4, 31000 Osijek, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1350-397X","authenticated-orcid":false,"given":"Ivan","family":"\u0106ori\u0107","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, Josipa Huttlera 4, 31000 Osijek, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7497-296X","authenticated-orcid":false,"given":"Ljubica","family":"Glava\u0161-Obrovac","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, Josipa Huttlera 4, 31000 Osijek, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9627-1598","authenticated-orcid":false,"given":"Aleksandra","family":"Torbica","sequence":"additional","affiliation":[{"name":"Institute of Food Technology in Novi Sad, University of Novi Sad, Bulevar cara Lazara 1, 21000 Novi Sad, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Roshandel, G., Ghasemi-Kebria, F., and Malekzadeh, R. (2025). Colorectal Cancer: Epidemiology, Risk Factors, and Prevention. Cancers, 16.","DOI":"10.3390\/cancers16081530"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Shaham, S.H., Vij, P., and Tripathi, M.K. (2025). Advances in Targeted and Chemotherapeutic Strategies for Colorectal Cancer: Current Insights and Future Directions. Biomedicines, 13.","DOI":"10.3390\/biomedicines13030642"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1080\/10717540490280778","article-title":"Polysaccharides for Colon-Targeted Drug Delivery","volume":"11","author":"Chourasia","year":"2004","journal-title":"Drug Deliv."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"79","DOI":"10.5001\/omj.2010.24","article-title":"Colon-Targeted Drug Delivery Systems: A Review on Primary and Novel Approaches","volume":"25","author":"Philip","year":"2010","journal-title":"Oman Med. J."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1021\/js970018g","article-title":"Chitosan capsules for colon-specific drug delivery: Improvement of insulin absorption from the rat colon","volume":"86","author":"Tozaki","year":"1997","journal-title":"J. Pharm. Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1002\/(SICI)1521-4184(19993)332:3<103::AID-ARDP103>3.0.CO;2-U","article-title":"Synthesis of chitosan succinate and chitosan phthalate and their evaluation as suggested matrices in an orally administered colon-specific drug delivery system","volume":"332","author":"Aiedeh","year":"1999","journal-title":"Arch. Pharm. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1023\/A:1018995029167","article-title":"In vitro evaluation of calcium pectinate: A potential colon-specific drug delivery carrier","volume":"10","author":"Rubinstein","year":"1993","journal-title":"Pharm. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1111\/j.2042-7158.1997.tb06856.x","article-title":"Studies on amidated pectins as potential carriers in colonic drug delivery","volume":"49","author":"Wakerly","year":"1997","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/S0928-0987(99)00087-1","article-title":"Development of Pectin Matrix Tablets for Colonic Delivery of the Model Drug Ropivacaine","volume":"10","author":"Ahrabi","year":"2000","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1208\/s12249-009-9253-y","article-title":"Chitosan\u2013Chondroitin Sulfate Based Matrix Tablets for Colon Specific Delivery of Indomethacin","volume":"10","author":"Amrutkar","year":"2009","journal-title":"AAPS PharmSciTech"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/j.ijbiomac.2014.12.052","article-title":"Calcium alginate-carboxymethyl cellulose beads for colon-targeted drug delivery","volume":"75","author":"Agarwal","year":"2015","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1023\/A:1011921925745","article-title":"Low-Swelling Crosslinked Guar and Its Potential Use as a Colon-Specific Drug Carrier","volume":"15","author":"Yagen","year":"1998","journal-title":"Pharm. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1080\/03639045.2020.1716375","article-title":"Development and Evaluation of Dapsone Tablets Coated for Specific Colon Release","volume":"46","author":"Barros","year":"2020","journal-title":"Drug Dev. Ind. Pharm."},{"key":"ref_14","first-page":"431","article-title":"Eudragit-S, Eudragit-L and Cellulose Acetate Phthalate Coated Polysaccharide Tablets for Colonic Targeted Delivery of Azathioprine","volume":"36","author":"Kotagale","year":"2010","journal-title":"Drug Dev. Ind. Pharm."},{"key":"ref_15","first-page":"17","article-title":"Formulation and in-vitro evaluation of dextrin matrix tablet of Ibuprofen for colon-specific drug delivery","volume":"21","author":"Salunkhe","year":"2008","journal-title":"Pak. J. Pharm. Sci."},{"key":"ref_16","first-page":"e33636","article-title":"Advances in Polysaccharide-Based Oral Colon-Targeted Delivery Systems: The Journey So Far and the Road Ahead","volume":"15","author":"Ibrahim","year":"2023","journal-title":"Cureus"},{"key":"ref_17","first-page":"100102","article-title":"Polysaccharides Carrier as Oral Colon-Specific Drug Delivery for Colon Cancer Treatment","volume":"10","author":"Musa","year":"2025","journal-title":"New Nano"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.ijpharm.2010.05.003","article-title":"Site-Specific Drug Delivery Systems within the Gastro-Intestinal Tract: From the Mouth to the Colon","volume":"395","author":"Pinto","year":"2010","journal-title":"Int. J. Pharm."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"5854","DOI":"10.1021\/acsomega.3c09156","article-title":"Biocompatible, Injectable, and Self-Healing Poly(N-vinylpyrrolidone)\/Carboxymethyl Cellulose Hydrogel for Drug Release","volume":"9","author":"Tang","year":"2024","journal-title":"ACS Omega"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/0168-3659(95)00049-E","article-title":"Dextran Hydrogels for Colon-Specific Drug Delivery","volume":"36","author":"Hovgaard","year":"1995","journal-title":"J. Control. Release"},{"key":"ref_21","first-page":"174","article-title":"Release Characteristics of Salmon Calcitonin from Dextran Hydrogels for Colon-Specific Delivery","volume":"64","author":"Basan","year":"2006","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"5082","DOI":"10.1021\/ma00118a042","article-title":"Characterization of the Network Structure of Dextran Glycidyl Methacrylate Hydrogels by Studying the Rheological and Swelling Behavior","volume":"28","author":"Lauwers","year":"1995","journal-title":"Macromolecules"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1007\/BF02973887","article-title":"Drug Release from the Enzyme-Degradable and pH-Sensitive Hydrogel Composed of Glycidyl Methacrylate Dextran and Poly(acrylic Acid)","volume":"28","author":"Kim","year":"2005","journal-title":"Arch. Pharm. Res."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Erceg, T., Radosavljevi\u0107, M., Milji\u0107, M., Cvetanovi\u0107 Kljaki\u0107, A., Balo\u0161, S., Mi\u0161kovi\u0107 \u0160poljari\u0107, K., \u0106ori\u0107, I., Glava\u0161-Obrovac, L., and Torbica, A. (2025). The Influence of Synthesis Parameters on the Properties of Dextran-Based Hydrogels for Colon-Targeted Antitumor Drug Delivery. Part I: Room Temperature Synthesis of Dextran\/Inulin Hydrogels for Colon-Targeted Antitumor Drug Delivery. Gels, 11.","DOI":"10.3390\/gels11121011"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Erceg, T.D., and Vuki\u0107, N.R. (2023). Architecture of Hydrogels. Hydrogels: Fundamentals to Advanced Energy Applications, CRC Press.","DOI":"10.1201\/9781003351566-5"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3737","DOI":"10.1007\/s10924-022-02473-7","article-title":"Synthesis and characterization of chitosan\u2013acrylic acid based hydrogels and investigation of the properties of bilayered design with incorporated alginate beads","volume":"30","author":"Erceg","year":"2022","journal-title":"J. Polym. Environ."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"100162","DOI":"10.1016\/j.microb.2024.100162","article-title":"Potential and prospects of reductases in azo dye degradation: A review","volume":"4","author":"Aragaw","year":"2024","journal-title":"Microbe"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1","DOI":"10.12974\/2311-8717.2024.12.01","article-title":"Development of dextran-coated zinc oxide nanoparticles with antimicrobial properties","volume":"12","author":"Ghegoiu","year":"2024","journal-title":"J. Compos. Biodegrad. Polym."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1186\/s12951-020-00714-2","article-title":"State-of-the-art polymeric nanoparticles as promising therapeutic tools against human bacterial infections","volume":"18","author":"Cano","year":"2020","journal-title":"J. Nanobiotechnol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"129310","DOI":"10.1016\/j.foodchem.2021.129310","article-title":"Polyphenol Bioaccessibility and Antioxidant Properties of In Vitro Digested Spray-Dried Thermally-Treated Skimmed Goat Milk Enriched with Pollen","volume":"351","year":"2021","journal-title":"Food Chem."},{"key":"ref_31","first-page":"31","article-title":"Partial Least Squares Method for Simultaneous Spectrophotometric Determination of Uracil and 5-Fluorouracil in Spiked Biological Samples","volume":"7","author":"Khajehsharifi","year":"2013","journal-title":"Appl. Chem. Today"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"\u0160uput, D., Pezo, L., Rakita, S., Spasevski, N., Tomi\u010di\u0107, R., Hormi\u0161, N., and Popovi\u0107, S. (2024). Camelina sativa Oilseed Cake as a Potential Source of Biopolymer Films: A Chemometric Approach to Synthesis, Characterization, and Optimization. Coatings, 14.","DOI":"10.3390\/coatings14010095"}],"container-title":["Gels"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2310-2861\/12\/1\/25\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T05:10:37Z","timestamp":1767676237000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2310-2861\/12\/1\/25"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,28]]},"references-count":32,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,1]]}},"alternative-id":["gels12010025"],"URL":"https:\/\/doi.org\/10.3390\/gels12010025","relation":{},"ISSN":["2310-2861"],"issn-type":[{"value":"2310-2861","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,28]]}}}