Design and Activity Evaluation of Berberine-Loaded Dual pH and Enzyme-Sensitive Colon-Targeting Microparticles
Ulcerative colitis (UC) is a multifactorial disorder, and conventional oral berberine (BBR) suffers from poor colonic targeting. This study aimed to develop a colon-targeted microparticle system (BBR-ES MPs) based on chitosan (CS) and Eudragit S-100 to enhance BBR delivery efficiency and therapeutic...
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2025-06-01
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| author | Jingqi Sun Xinlong Chai Xiwen Zeng Qingwei Wang Yanwen Ling Lihong Wang Jin Su |
| author_facet | Jingqi Sun Xinlong Chai Xiwen Zeng Qingwei Wang Yanwen Ling Lihong Wang Jin Su |
| author_sort | Jingqi Sun |
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| description | Ulcerative colitis (UC) is a multifactorial disorder, and conventional oral berberine (BBR) suffers from poor colonic targeting. This study aimed to develop a colon-targeted microparticle system (BBR-ES MPs) based on chitosan (CS) and Eudragit S-100 to enhance BBR delivery efficiency and therapeutic efficacy in UC. <b>Methods</b>: BBR-CS nanocarriers were prepared via ionotropic gelation and coated with Eudragit S-100 to form pH/enzyme dual-responsive MPs. Colon-targeting performance was validated through in vitro release assays. SPF-grade male KM mice (Ethics Approval No.: JMSU-2021090301) with dextran sulfate sodium (DSS)-induced UC were divided into normal, model, BBR, and BBR-ES MPs groups. Therapeutic outcomes were evaluated by monitoring body weight, disease activity index (DAI), colon length, histopathology, inflammatory cytokines (IL-1β, IL-6, TNF-α, IL-10), and myeloperoxidase (MPO) activity via ELISA. Gut microbiota diversity was analyzed using 16S rRNA sequencing. <b>Results</b>: BBR-ES MP treatment significantly reduced DAI scores (<i>p</i> < 0.01), restored colon length, downregulated pro-inflammatory cytokines (IL-1β, IL-6, TNF-α; <i>p</i> < 0.05), and upregulated anti-inflammatory IL-10. Microbiota analysis revealed that the Bacteroidetes/Firmicutes ratio, which decreased in the model group, was restored post-treatment, with alpha/beta diversity approaching normal levels. BBR-ES MPs outperformed free BBR at equivalent doses. <b>Conclusion</b>: BBR-ES MPs achieved colon-targeted drug delivery via pH/enzyme dual-responsive mechanisms, effectively alleviating UC inflammation and modulating gut dysbiosis, offering a safe and precise therapeutic strategy for UC management. |
| format | Article |
| id | doaj-art-464cb3dc821f46b79bc4636c615acc03 |
| institution | OA Journals |
| issn | 1999-4923 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | MDPI AG |
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| series | Pharmaceutics |
| spelling | doaj-art-464cb3dc821f46b79bc4636c615acc032025-08-20T02:21:50ZengMDPI AGPharmaceutics1999-49232025-06-0117677810.3390/pharmaceutics17060778Design and Activity Evaluation of Berberine-Loaded Dual pH and Enzyme-Sensitive Colon-Targeting MicroparticlesJingqi Sun0Xinlong Chai1Xiwen Zeng2Qingwei Wang3Yanwen Ling4Lihong Wang5Jin Su6 Department of Pharmaceutics, School of Pharmacy, China Jiamusi University, Jiamusi 154007, China Department of Pharmaceutics, School of Pharmacy, China Jiamusi University, Jiamusi 154007, China Department of Pharmaceutics, School of Pharmacy, China Jiamusi University, Jiamusi 154007, China Department of Pharmaceutics, School of Pharmacy, China Jiamusi University, Jiamusi 154007, China Department of Pharmaceutics, School of Pharmacy, China Jiamusi University, Jiamusi 154007, China Department of Pharmaceutics, School of Pharmacy, China Jiamusi University, Jiamusi 154007, China Department of Pharmaceutics, School of Pharmacy, China Jiamusi University, Jiamusi 154007, ChinaUlcerative colitis (UC) is a multifactorial disorder, and conventional oral berberine (BBR) suffers from poor colonic targeting. This study aimed to develop a colon-targeted microparticle system (BBR-ES MPs) based on chitosan (CS) and Eudragit S-100 to enhance BBR delivery efficiency and therapeutic efficacy in UC. <b>Methods</b>: BBR-CS nanocarriers were prepared via ionotropic gelation and coated with Eudragit S-100 to form pH/enzyme dual-responsive MPs. Colon-targeting performance was validated through in vitro release assays. SPF-grade male KM mice (Ethics Approval No.: JMSU-2021090301) with dextran sulfate sodium (DSS)-induced UC were divided into normal, model, BBR, and BBR-ES MPs groups. Therapeutic outcomes were evaluated by monitoring body weight, disease activity index (DAI), colon length, histopathology, inflammatory cytokines (IL-1β, IL-6, TNF-α, IL-10), and myeloperoxidase (MPO) activity via ELISA. Gut microbiota diversity was analyzed using 16S rRNA sequencing. <b>Results</b>: BBR-ES MP treatment significantly reduced DAI scores (<i>p</i> < 0.01), restored colon length, downregulated pro-inflammatory cytokines (IL-1β, IL-6, TNF-α; <i>p</i> < 0.05), and upregulated anti-inflammatory IL-10. Microbiota analysis revealed that the Bacteroidetes/Firmicutes ratio, which decreased in the model group, was restored post-treatment, with alpha/beta diversity approaching normal levels. BBR-ES MPs outperformed free BBR at equivalent doses. <b>Conclusion</b>: BBR-ES MPs achieved colon-targeted drug delivery via pH/enzyme dual-responsive mechanisms, effectively alleviating UC inflammation and modulating gut dysbiosis, offering a safe and precise therapeutic strategy for UC management.https://www.mdpi.com/1999-4923/17/6/778berberinecolonic targetingparticlesulcerative colitisintestinal flora |
| spellingShingle | Jingqi Sun Xinlong Chai Xiwen Zeng Qingwei Wang Yanwen Ling Lihong Wang Jin Su Design and Activity Evaluation of Berberine-Loaded Dual pH and Enzyme-Sensitive Colon-Targeting Microparticles Pharmaceutics berberine colonic targeting particles ulcerative colitis intestinal flora |
| title | Design and Activity Evaluation of Berberine-Loaded Dual pH and Enzyme-Sensitive Colon-Targeting Microparticles |
| title_full | Design and Activity Evaluation of Berberine-Loaded Dual pH and Enzyme-Sensitive Colon-Targeting Microparticles |
| title_fullStr | Design and Activity Evaluation of Berberine-Loaded Dual pH and Enzyme-Sensitive Colon-Targeting Microparticles |
| title_full_unstemmed | Design and Activity Evaluation of Berberine-Loaded Dual pH and Enzyme-Sensitive Colon-Targeting Microparticles |
| title_short | Design and Activity Evaluation of Berberine-Loaded Dual pH and Enzyme-Sensitive Colon-Targeting Microparticles |
| title_sort | design and activity evaluation of berberine loaded dual ph and enzyme sensitive colon targeting microparticles |
| topic | berberine colonic targeting particles ulcerative colitis intestinal flora |
| url | https://www.mdpi.com/1999-4923/17/6/778 |
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