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藻酸盐/羧甲基壳聚糖微珠用于塞来昔布缓释及体外减轻肠道炎症的优化

Optimization of alginate/carboxymethyl chitosan microbeads for the sustained release of celecoxib and attenuation of intestinal inflammation in vitro.

作者信息

Biji Catherin Ann, Balde Akshad, Kim Se-Kwon, Nazeer Rasool Abdul

机构信息

Biopharmaceuticals Lab, Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur 603 203, Tamilnadu, India.

Department of Marine Science and Convergence Engineering, Hanyang University, Ansan 11558, Gyeonggi-do, South Korea.

出版信息

Int J Biol Macromol. 2024 Dec;282(Pt 3):137022. doi: 10.1016/j.ijbiomac.2024.137022. Epub 2024 Oct 29.

Abstract

Multiple anti-inflammatory medications have helped treat inflammatory bowel disease (IBD). However, oral administration has minimal absorption and systemic side effects. This study aims to investigate the potential of encapsulating anti-inflammatory drug celecoxib (Cele) within microbeads for the treatment of IBD. Microbeads were formed by cross-linking carboxymethyl chitosan (CMCs) with sodium alginate (Alg) through the ionic gelation method and optimized through response surface methodology. Additionally, the study revealed a mucoadhesivity value of 59.32 ± 0.74 % for the optimized microbead system. The drug release study demonstrated the sustained release of Cele CMCs/Alg microbeads upto 24 h compared to quick release of the free drug. The results of the cell viability assay indicated that the Cele-Alg/CMCs microbeads exhibited a non-toxic nature within the concentration range of 100-250 μM. A significant decrease in nitric oxide (NO) generation (61.14 ± 3.67 %) was seen in HCT-116 cells stimulated with lipopolysaccharide (LPS) upon treatment with Cele-250/CMCs/Alg microbeads. The results of the reactive oxygen species and wound healing assay suggest that Cele-250/CMCs/Alg microbeads had improved anti-inflammatory characteristics comparable to those of free drug treatment. The western blot analysis demonstrated that the microbeads composed of CMCs/Alg-Cele possess the capacity to inhibit the expression of COX-2 in vitro supressing inflammation.

摘要

多种抗炎药物有助于治疗炎症性肠病(IBD)。然而,口服给药吸收极少且有全身副作用。本研究旨在探讨将抗炎药物塞来昔布(Cele)包裹于微珠中用于治疗IBD的潜力。微珠通过离子凝胶法将羧甲基壳聚糖(CMCs)与海藻酸钠(Alg)交联形成,并通过响应面法进行优化。此外,该研究显示优化后的微珠系统的黏膜黏附值为59.32±0.74%。药物释放研究表明,与游离药物的快速释放相比,Cele CMCs/Alg微珠可持续释放长达24小时。细胞活力测定结果表明,Cele-Alg/CMCs微珠在100 - 250μM浓度范围内表现出无毒特性。在用Cele-250/CMCs/Alg微珠处理后,在用脂多糖(LPS)刺激的HCT-116细胞中,一氧化氮(NO)生成显著减少(61.14±3.67%)。活性氧和伤口愈合测定结果表明,Cele-250/CMCs/Alg微珠具有与游离药物治疗相当的改善的抗炎特性。蛋白质印迹分析表明,由CMCs/Alg-Cele组成的微珠具有在体外抑制COX-2表达从而抑制炎症的能力。

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