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用于临床前炎症性肠病的结肠靶向壳聚糖-褪黑素纳米疗法。

Colon targeted chitosan-melatonin nanotherapy for preclinical Inflammatory Bowel Disease.

机构信息

Chemical Biology Unit, Institute of Nano Science and Technology (INST), Sector-81, Knowledge City, SAS Nagar, Punjab 140306, India.

Disease Biology Laboratory, Regional Centre for Biotechnology (RCB), National Capital Region Biotech Science Cluster, Faridabad, Haryana 121001, India.

出版信息

Biomater Adv. 2022 May;136:212796. doi: 10.1016/j.bioadv.2022.212796. Epub 2022 Apr 11.

DOI:10.1016/j.bioadv.2022.212796
PMID:35929295
Abstract

Inflammatory Bowel (IBD) is an umbrella term which includes Crohn's Disease (CD) and Ulcerative Colitis (UC). At present, therapies available for management of the UC includes, corticosteroid, immuno-suppressants and antibiotics are used for mild to moderate UC conditions which can cause nephrotoxicity, hepatotoxicity and cardiotoxicity. Hence, a novel therapeutic candidate having potent anti-inflammatory effect is urgently warranted for the management of UC. Melatonin has emerged as a potent anti-inflammatory agent. However, poor solubility limits its therapeutic potential. Therefore, colon targeted Eudragit-S-100 coated chitosan nanoparticles have been demonstrated to improve melatonin therapeutic efficacy. It was found that melatonin loaded chitosan and colon targeted chitosan nanoparticles had promising anti-inflammatory efficacy in terms of NO scavenging activity in an in-vitro LPS challenged macrophages. Also, colon targeted oral chitosan nano-formulation exhibited remarkable protection in an in vivo UC mice model by improving gross pathological parameters, histo-architectural protection, goblet cell depletion, and immune cells infiltration which can be extrapolated to clinical studies.

摘要

炎症性肠病(IBD)是一个总称,包括克罗恩病(CD)和溃疡性结肠炎(UC)。目前,用于 UC 管理的治疗方法包括皮质类固醇、免疫抑制剂和抗生素,用于轻度至中度 UC 病症,这些药物可能会引起肾毒性、肝毒性和心脏毒性。因此,迫切需要一种具有强大抗炎作用的新型治疗候选药物来治疗 UC。褪黑素已成为一种有效的抗炎剂。然而,较差的溶解性限制了其治疗潜力。因此,已经证明结肠靶向 Eudragit-S-100 包衣壳聚糖纳米粒可以提高褪黑素的治疗效果。研究发现,褪黑素负载的壳聚糖和结肠靶向壳聚糖纳米粒在体外 LPS 刺激的巨噬细胞中具有良好的 NO 清除活性,具有有前途的抗炎功效。此外,结肠靶向口服壳聚糖纳米制剂通过改善大体病理参数、组织形态保护、杯状细胞耗竭和免疫细胞浸润,在体内 UC 小鼠模型中表现出显著的保护作用,这可以推断到临床研究中。

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