Wang Mo, Jiang Yu, Chen Zhiyang, Jiang Dengbao, Jiang Xuan, Ye Jun, Wang Hongliang, Liu Yuling
State 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, China.
Beijing Key Laboratory of Drug Delivery Technology and Novel Formulation, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
Molecules. 2025 Apr 23;30(9):1878. doi: 10.3390/molecules30091878.
Ulcerative colitis (UC) is a chronic inflammation disease with severe impact on quality of life, with limited treatment options. 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.
溃疡性结肠炎（UC）是一种对生活质量有严重影响的慢性炎症性疾病，治疗选择有限。桑叶中的生物碱（SZ-A）因其安全性和药理作用（包括抗炎和屏障修复）而有望用于UC治疗。然而，由于其作为口服后靶向小肠的α-葡萄糖苷酶抑制剂的药理作用，其临床应用受到胃肠胀气副作用的限制。因此，构建一种结肠靶向制剂来递送SZ-A是改善UC治疗的有利策略。在本研究中，我们使用具有粘膜粘附和炎症靶向特性的硫醇化透明质酸与SZ-A形成的复合物作为中间载体，并采用双乳液法制备了海藻酸钠修饰的PLGA微球（SZ-A@MSs），以实现SZ-A的高效包封。具体而言，海藻酸钠作为胃酸保护剂和微生物群响应材料，使微球在结肠区域能够精确且响应性地释放。SZ-A@MSs的粒径约为30 µm，载药量约为12.0%，包封率约为31.7%，通过肠道粘附和靶向炎症部位发挥作用。SZ-A@MSs在Raw264.7细胞中表现出抗氧化和抗炎能力。体内成像结果表明，SZ-A@MSs具有良好的结肠部位滞留和缓释效果。药效学结果表明，SZ-A@MSs显示出良好的疗效，包括抑制体重减轻、抑制结肠萎缩和抑制炎症因子分泌的能力。总之，SZ-A@MSs具有良好的结肠靶向特性，可提高治疗效果，为UC提供了一种潜在的治疗方法。
