Colon-Targeted Mucoadhesive PLGA Microspheres Loaded with Ramulus Mori Alkaloids for Enhanced Water-Soluble Drug Delivery in Ulcerative Colitis Treatment

作者：Mo Wang, Yu Jiang, Zhiyang Chen, Dengbao Jiang, Xuan Jiang, Jun Ye, Hongliang Wang, Yuling Liu · 发表于：Molecules · 年份：2025 · DOI：10.3390/molecules30091878 · 被引用次数：5 · 研究领域：Inflammatory Bowel Disease、Gastrointestinal motility and disorders、Gut microbiota and health

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 l...