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通过益生元纳米颗粒联合调节肠道微生物群和酶触发的结肠给药可改善小鼠结肠炎治疗。

Combining Gut Microbiota Modulation and Enzymatic-Triggered Colonic Delivery by Prebiotic Nanoparticles Improves Mouse Colitis Therapy.

作者信息

Li Hui, Cheng Yu, Cui Luwen, Yang Zizhen, Wang Jingyi, Zhang Zixuan, Chen Kaiwei, Zhao Cheng, He Ningning, Li Shangyong

机构信息

School of Basic Medicine, Qingdao Medical College, Qingdao University, Qingdao, China.

Department of Abdominal Ultrasound, The Affiliated Hospital of Qingdao University, Qingdao, China.

出版信息

Biomater Res. 2024 Aug 13;28:0062. doi: 10.34133/bmr.0062. eCollection 2024.

DOI:10.34133/bmr.0062
PMID:39140035
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11321063/
Abstract

The efficacy of ulcerative colitis (UC) therapy is closely connected to the composition of gut microbiota in the gastrointestinal tract. Prebiotic-based nanoparticles (NPs) provide a more precise approach to alleviate UC via modulating gut microbiota dysbiosis. The present study develops an efficient prebiotic-based colon-targeted drug delivery system (PCDDS) by using prebiotic pectin (Pcn) and chitosan (Csn) polysaccharides as a prebiotic shell, with the anti-inflammatory drug sulfasalazine (SAS) loaded into a poly(lactic-co-glycolic acid) (PLGA) core to construct SAS@PLGA-Csn-Pcn NPs. Then, we examine its characterization, cellular uptake, and in vivo therapeutic efficacy. The results of our study indicate that the Pcn/Csn shell confers efficient pH-sensitivity properties. The gut microbiota-secreted pectinase serves as the trigger agent for Pcn/Csn shell degradation, and the resulting Pcn oligosaccharides possess a substantial prebiotic property. Meanwhile, the formed PCDDSs exhibit robust biodistribution and accumulation in the colon tissue, rapid cellular uptake, efficient in vivo therapeutic efficacy, and modulation of gut microbiota dysbiosis in a mouse colitis model. Collectively, our synthetic PCDDSs demonstrate a promising and synergistic strategy for UC therapy.

摘要

溃疡性结肠炎(UC)治疗的疗效与胃肠道中肠道微生物群的组成密切相关。基于益生元的纳米颗粒(NPs)通过调节肠道微生物群失调,为缓解UC提供了一种更精确的方法。本研究通过使用益生元果胶(Pcn)和壳聚糖(Csn)多糖作为益生元外壳,开发了一种高效的基于益生元的结肠靶向给药系统(PCDDS),将抗炎药物柳氮磺胺吡啶(SAS)负载到聚乳酸-乙醇酸共聚物(PLGA)核中,构建了SAS@PLGA-Csn-Pcn NPs。然后,我们研究了其特性、细胞摄取和体内治疗效果。我们的研究结果表明,Pcn/Csn外壳具有高效的pH敏感性。肠道微生物群分泌的果胶酶作为Pcn/Csn外壳降解的触发剂,产生的Pcn寡糖具有显著的益生元特性。同时,形成的PCDDSs在结肠组织中表现出强大的生物分布和积累、快速的细胞摄取、高效的体内治疗效果以及对小鼠结肠炎模型中肠道微生物群失调的调节作用。总的来说,我们合成的PCDDSs为UC治疗展示了一种有前景的协同策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da66/11321063/473cab5eecfc/bmr.0062.fig.007.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da66/11321063/4bad3ad9a422/bmr.0062.fig.002.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da66/11321063/473cab5eecfc/bmr.0062.fig.007.jpg

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