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载有鼠李糖乳杆菌 GG 的海藻酸钠/壳聚糖双层微凝胶的口服给药用于溃疡性结肠炎的靶向治疗。

Oral delivery of sodium alginate/chitosan bilayer microgels loaded with Lactobacillus rhamnosus GG for targeted therapy of ulcerative colitis.

机构信息

School of Pharmaceutical Science, South-Central MinZu University, Wuhan 430074, PR China.

Xinjiang Key Laboratory of Hotan Characteristic Traditional Chinese Medicine Research, College of Xinjiang Uyghur Medicine, Hotan 848000, PR China.

出版信息

Int J Biol Macromol. 2024 Oct;278(Pt 3):134785. doi: 10.1016/j.ijbiomac.2024.134785. Epub 2024 Aug 15.

DOI:10.1016/j.ijbiomac.2024.134785
PMID:39153668
Abstract

Probiotics regulate intestinal flora balance and enhance the intestinal barrier, which is useful in preventing and treating colitis. However, they have strict storage requirements. In addition, they degrade in a strongly acidic environment, resulting in a significant decrease in their activity when used as microbial agents. Lactobacillus rhamnosus GG (LGG) was loaded into acid-resistant and colon-targeting double-layer microgels. The inner layer consists of guar gum (GG) and low methoxyl pectin (LMP), which can achieve retention and degradation in the colon. To achieve colon localization, the outer layer was composed of chitosan (CS) and sodium alginate (SA). The formulation demonstrated favorable bio-responses across various pH conditions in vitro and sustained release of LGG in the colon lesions. Bare LGG survival decreased by 52.2 % in simulated gastric juice (pH 1.2) for 2 h, whereas that of encapsulated LGG decreased by 18.5 %. In the DSS-induced inflammatory model, LGG-loaded microgel significantly alleviated UC symptoms in mice and reduced inflammatory factor levels in the colon. Encapsulation of LGG improved its stability in acidic conditions, thus increasing its content at the colon lesions and reducing pathogenic bacteria. These findings provide an experimental basis and a technical reference for developing and applying probiotic microgel preparations.

摘要

益生菌可调节肠道菌群平衡,增强肠道屏障,有助于预防和治疗结肠炎。但是,它们对存储条件要求严格。此外,它们在强酸性环境中会降解,用作微生物制剂时其活性会显著降低。将鼠李糖乳杆菌 GG(LGG)载入耐酸和结肠靶向双层微凝胶中。内层由瓜尔胶(GG)和低甲氧基果胶(LMP)组成,可在结肠中保留和降解。为了实现结肠定位,外层由壳聚糖(CS)和海藻酸钠(SA)组成。该配方在体外的各种 pH 值条件下表现出良好的生物响应,并且在结肠病变部位持续释放 LGG。在模拟胃液(pH 1.2)中孵育 2 小时后,裸 LGG 的存活率下降了 52.2%,而包封的 LGG 仅下降了 18.5%。在 DSS 诱导的炎症模型中,载 LGG 的微凝胶可显著减轻小鼠 UC 症状并降低结肠中的炎症因子水平。LGG 的包封提高了其在酸性条件下的稳定性,从而增加了其在结肠病变部位的含量,并减少了致病菌。这些发现为开发和应用益生菌微凝胶制剂提供了实验依据和技术参考。

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