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In this study, pH-sensitive, core\u2013shell hydrogel microcapsules were designed and fabricated using a BUCHI B-390 microsphere preparation device via electrostatic interactions and hydrogen bonds. Olsalazine sodium was encapsulated in the microcapsules, allowing for pH-responsive drug release in colon tissue for UC treatment in mice. XRD studies demonstrated the amorphous state of the drug in the formulation. The preparation of SCO microcapsules was optimized based on the drug encapsulation efficiency and the drug loading capacity, with the S2C1O microcapsule having the highest drug encapsulation efficiency (59.2%) and drug loading capacity (21.3%), and the production yield was approximately 62.5%. The degradation experiment results indicated that the alginate\/CMCS hydrogel shell has anti-resistant and colon-targeted properties, with minimal drug leakage under acidic conditions (0.1% release at 2 h, pH 1.2) and rapid, controlled release at colonic pH (7.4) (cumulative release of 68.7% at 12 h), protecting the drug from gastric degradation. An in vivo experiment suggested that treatment with these microcapsules in UC mice significantly reduced inflammatory markers (NF-\u03baB p65 was reduced by 18.8% relative to the free drug group) and histological damage in UC models relative to free drug administration. The improved therapeutic efficacy is linked to precise localization in inflamed tissue, reducing systemic exposure and off-target effects. Overall, in vitro and in vivo studies demonstrated that this microcapsule system provides a promising alternative to existing UC drug delivery systems.<\/jats:p>","DOI":"10.3390\/gels12080718","type":"journal-article","created":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T09:31:09Z","timestamp":1786613469000},"page":"718","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Efficient Preparation of pH-Sensitive Core\u2013Shell Drug-Loaded Hydrogel Microcapsules and Their Application in Ulcerative Colitis Treatment"],"prefix":"10.3390","volume":"12","author":[{"given":"Qingqing","family":"Xue","sequence":"first","affiliation":[{"name":"Key Laboratory of Biotechnology and Bioengineering of State Ethnic Affairs Commission, Biomedical Research Center, Engineering Research Center of Key Technology and Industrialization of Cell-Based Vaccine, Ministry of Education, Gansu Tech Innovation Center of Animal Cell, 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