Ma Huilin, Li Yunmei, Shi Huan, Wang Biaobiao, Tian He, Mei Xifan, Wu Chao
Pharmacy School, Jinzhou Medical University, Jinzhou, China; Liaoning Provincial Collaborative Innovation Center for Medical Testing and Drug Research, Jinzhou Medical University, Jinzhou, China.
Liaoning Provincial Collaborative Innovation Center for Medical Testing and Drug Research, Jinzhou Medical University, Jinzhou, China; School of Basic Medicine, Jinzhou Medical University, Jinzhou, China.
Int J Biol Macromol. 2025 Mar;294:139114. doi: 10.1016/j.ijbiomac.2024.139114. Epub 2025 Jan 2.
In this study, we developed calcium alginate-coated nanovesicles derived from macrophage membranes loaded with berberine (Ber@MVs-CA) for the oral treatment of ulcerative colitis (UC). Ber@MVs-CA demonstrates resistance to gastric acid and controlled drug release in the colonic pH environment, while actively targeting sites of ulcerative colitis injury. pH-responsive release of Ber in Ber@MVs-CA was confirmed through in vitro release experiments. The results indicated a total of 19.35 ± 1.61 % of Ber was cumulatively released from Ber@MVs-CA in SGF and SIF at 4 h, and approximately 87.14 ± 2.33 % release in simulated colonic fluid (pH 7.4) after 24 h. The targeting ability of Ber@MVs-CA was confirmed using laser confocal microscopy (CLSM), Transwell™ system, and in vivo imaging. Results demonstrated effective targeting of inflammatory macrophages and sustained retention in the colon. In vitro and in vivo (mice) assessments via immunofluorescence, ELISA kit, and reactive oxygen species (ROS) assays demonstrated that Ber@MVs-CA effectively attenuated inflammatory responses, modulated macrophage polarization, and inhibited oxidative stress. Additionally, we evaluated the therapeutic efficacy of Ber@MVs-CA in a Clostridium perfringens-induced enteritis model in chickens, demonstrating its effectiveness in alleviating enteritis. Consequently, Ber@MVs-CA exhibits great potential as an oral nano-formulation for the treatment of enteritis. Thus, Ber@MVs-CA shows great potential as an oral nano-formulation for the treatment of enteritis.
在本研究中,我们制备了负载黄连素的巨噬细胞膜衍生的海藻酸钙包被纳米囊泡(Ber@MVs-CA)用于溃疡性结肠炎(UC)的口服治疗。Ber@MVs-CA对胃酸具有抗性,并在结肠pH环境中实现药物控释,同时能主动靶向溃疡性结肠炎损伤部位。通过体外释放实验证实了Ber@MVs-CA中黄连素的pH响应性释放。结果表明,在模拟胃液(SGF)和模拟肠液(SIF)中,4小时时Ber@MVs-CA中累计释放的黄连素总量为19.35±1.61%,在模拟结肠液(pH 7.4)中24小时后释放量约为87.14±2.33%。使用激光共聚焦显微镜(CLSM)、Transwell™系统和体内成像证实了Ber@MVs-CA的靶向能力。结果表明其能有效靶向炎症巨噬细胞并在结肠中持续保留。通过免疫荧光、ELISA试剂盒和活性氧(ROS)检测进行的体外和体内(小鼠)评估表明,Ber@MVs-CA能有效减轻炎症反应、调节巨噬细胞极化并抑制氧化应激。此外,我们在产气荚膜梭菌诱导的鸡肠炎模型中评估了Ber@MVs-CA的治疗效果,证明其在减轻肠炎方面的有效性。因此,Ber@MVs-CA作为治疗肠炎的口服纳米制剂具有巨大潜力。因此,Ber@MVs-CA作为治疗肠炎的口服纳米制剂显示出巨大潜力。