Colon-Targeted Mucoadhesive PLGA Microspheres Loaded with <i>Ramulus Mori</i> Alkaloids for Enhanced Water-Soluble Drug Delivery in Ulcerative Colitis Treatment
Ulcerative colitis (UC) is a chronic inflammation disease with severe impact on quality of life, with limited treatment options. <i>Ramulus Mori</i> alkaloids (SZ-A) from Morus alba show promise for UC treatment due to their safety and pharmacological effects, including anti-inflammation...
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MDPI AG
2025-04-01
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| author | Mo Wang Yu Jiang Zhiyang Chen Dengbao Jiang Xuan Jiang Jun Ye Hongliang Wang Yuling Liu |
| author_facet | Mo Wang Yu Jiang Zhiyang Chen Dengbao Jiang Xuan Jiang Jun Ye Hongliang Wang Yuling Liu |
| author_sort | Mo Wang |
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| description | Ulcerative colitis (UC) is a chronic inflammation disease with severe impact on quality of life, with limited treatment options. <i>Ramulus Mori</i> alkaloids (SZ-A) from Morus alba show promise for UC treatment due to their safety and pharmacological effects, including anti-inflammation and barrier repair. However, their clinical use has been limited by gastrointestinal flatulence as a side effect due to their pharmacological action as an α-glucosidase inhibitor targeting the small intestine following oral administration. Therefore, constructing a colon-targeted formulation to deliver SZ-A is an advantageous strategy to improve UC therapy. In this study, we used the complex formed by thiolated hyaluronic acid, which has mucosal adhesion and inflammation-targeting properties, and SZ-A as an intermediate carrier and prepared sodium alginate-modified PLGA microspheres (SZ-A@MSs) with the double emulsion method to achieve efficient encapsulation of SZ-A. Specifically, sodium alginate serves as a gastric acid protectant and microbiota-responsive material, enabling the precise and responsive release of microspheres in the colonic region. SZ-A@MSs have a particle size of about 30 µm, a drug loading of about 12.0%, and an encapsulation efficiency of about 31.7% and function through intestinal adhesion to and targeting of inflammatory sites. SZ-A@MSs showed antioxidant and anti-inflammatory abilities in Raw264.7 cells. In vivo imaging results suggest that SZ-A@MSs have good colon site retention and sustained-release effect. Pharmacodynamic results show that SZ-A@MSs display good efficacy, including the ability to inhibit weight loss, inhibit colonic atrophy, and inhibit the secretion of inflammatory factors. In conclusion, SZ-A@MSs have good colon-targeting properties, can improve therapeutic effects, and provide a potential treatment method for UC. |
| format | Article |
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| language | English |
| publishDate | 2025-04-01 |
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| series | Molecules |
| spelling | doaj-art-dc4e4ed37b6c42168a1490d1b10abb122025-08-20T02:58:47ZengMDPI AGMolecules1420-30492025-04-01309187810.3390/molecules30091878Colon-Targeted Mucoadhesive PLGA Microspheres Loaded with <i>Ramulus Mori</i> Alkaloids for Enhanced Water-Soluble Drug Delivery in Ulcerative Colitis TreatmentMo Wang0Yu Jiang1Zhiyang Chen2Dengbao Jiang3Xuan Jiang4Jun Ye5Hongliang Wang6Yuling Liu7State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, ChinaState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, ChinaState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, ChinaState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, ChinaState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, ChinaState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, ChinaState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, ChinaState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, ChinaUlcerative colitis (UC) is a chronic inflammation disease with severe impact on quality of life, with limited treatment options. <i>Ramulus Mori</i> alkaloids (SZ-A) from Morus alba show promise for UC treatment due to their safety and pharmacological effects, including anti-inflammation and barrier repair. However, their clinical use has been limited by gastrointestinal flatulence as a side effect due to their pharmacological action as an α-glucosidase inhibitor targeting the small intestine following oral administration. Therefore, constructing a colon-targeted formulation to deliver SZ-A is an advantageous strategy to improve UC therapy. In this study, we used the complex formed by thiolated hyaluronic acid, which has mucosal adhesion and inflammation-targeting properties, and SZ-A as an intermediate carrier and prepared sodium alginate-modified PLGA microspheres (SZ-A@MSs) with the double emulsion method to achieve efficient encapsulation of SZ-A. Specifically, sodium alginate serves as a gastric acid protectant and microbiota-responsive material, enabling the precise and responsive release of microspheres in the colonic region. SZ-A@MSs have a particle size of about 30 µm, a drug loading of about 12.0%, and an encapsulation efficiency of about 31.7% and function through intestinal adhesion to and targeting of inflammatory sites. SZ-A@MSs showed antioxidant and anti-inflammatory abilities in Raw264.7 cells. In vivo imaging results suggest that SZ-A@MSs have good colon site retention and sustained-release effect. Pharmacodynamic results show that SZ-A@MSs display good efficacy, including the ability to inhibit weight loss, inhibit colonic atrophy, and inhibit the secretion of inflammatory factors. In conclusion, SZ-A@MSs have good colon-targeting properties, can improve therapeutic effects, and provide a potential treatment method for UC.https://www.mdpi.com/1420-3049/30/9/1878ulcerative colitis<i>Ramulus Mori</i> alkaloidsmicrosphereanti-inflammatoryPLGA |
| spellingShingle | Mo Wang Yu Jiang Zhiyang Chen Dengbao Jiang Xuan Jiang Jun Ye Hongliang Wang Yuling Liu Colon-Targeted Mucoadhesive PLGA Microspheres Loaded with <i>Ramulus Mori</i> Alkaloids for Enhanced Water-Soluble Drug Delivery in Ulcerative Colitis Treatment Molecules ulcerative colitis <i>Ramulus Mori</i> alkaloids microsphere anti-inflammatory PLGA |
| title | Colon-Targeted Mucoadhesive PLGA Microspheres Loaded with <i>Ramulus Mori</i> Alkaloids for Enhanced Water-Soluble Drug Delivery in Ulcerative Colitis Treatment |
| title_full | Colon-Targeted Mucoadhesive PLGA Microspheres Loaded with <i>Ramulus Mori</i> Alkaloids for Enhanced Water-Soluble Drug Delivery in Ulcerative Colitis Treatment |
| title_fullStr | Colon-Targeted Mucoadhesive PLGA Microspheres Loaded with <i>Ramulus Mori</i> Alkaloids for Enhanced Water-Soluble Drug Delivery in Ulcerative Colitis Treatment |
| title_full_unstemmed | Colon-Targeted Mucoadhesive PLGA Microspheres Loaded with <i>Ramulus Mori</i> Alkaloids for Enhanced Water-Soluble Drug Delivery in Ulcerative Colitis Treatment |
| title_short | Colon-Targeted Mucoadhesive PLGA Microspheres Loaded with <i>Ramulus Mori</i> Alkaloids for Enhanced Water-Soluble Drug Delivery in Ulcerative Colitis Treatment |
| title_sort | colon targeted mucoadhesive plga microspheres loaded with i ramulus mori i alkaloids for enhanced water soluble drug delivery in ulcerative colitis treatment |
| topic | ulcerative colitis <i>Ramulus Mori</i> alkaloids microsphere anti-inflammatory PLGA |
| url | https://www.mdpi.com/1420-3049/30/9/1878 |
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