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Science Bulletin · 2019 · IF 6.277

Biomimetic intestinal barrier based on microfluidic encapsulated sucralfate microcapsules

Cheng Zhao,Yunru Yu,Xiaoxuan Zhang,Xiuwen Wu,Jianan Ren,Yuanjin Zhao

Intestinal barriers play an important role in preventing intestinally derived diseases, and maintaining their function is a promising approach to prevent and treat those diseases. Here, inspired by the protection effect of intestinal barriers in live organisms and the mucosa adhesive property of sucralfate, we present a biomimetic intestinal barrier based on microfluidic encapsulated sucralfate microcapsules. Benefiting from the flexible selectivity and precise control of microfluidic electrospray flows, the generated microcapsules were imparted with stomach-tolerant dietary-fibre shells and controllable released sucralfate cores, both of which could contribute to forming a continuous biomimetic intestinal barrier on the intestine. Through in vitro adhesive study, in vivo computed tomography (CT) imaging and in vivo imaging system (IVIS) methods, we have demonstrated that the microcapsule-derived biomimetic intestinal barrier can effectively block food fermentation in the gut, reduce generation of fat, decrease disease risk indexes, and prevent obesity. These features make the microfluidic encapsulated sucralfate microcapsules and their resultant biomimetic intestinal barrier an approach for treating obesity and other intestinal diseases.

研究领域: 生物医学工程 · 药剂学 · 消化系统研究
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Scientific Reports · 2024 ·Vol. 14 ·期 1 ·1-12 · IF 3.8

Probiotic potential of Lacticaseibacillus rhamnosus VHProbi M15 on sucralfate-induced constipation in mice

Cheng Shumin,Cui Hongchang,Zhang Jingyan,Wang Qian,Duan Zhi

The main objective of this study was to investigate the potential probiotic properties of Lacticaseibacillus rhamnosus VHProbi®M15 (M15). This study examined the effects of M15 on sucralfate-induced constipation in a mouse model. The BALB/c mice were randomly divided into four groups: the normal group (NOR) was without any treatment, while the constipation (CON), phenolphthalein (PHE), and probiotic (PRO) treatment groups were fed with sucralfate until the appearance of constipation symptoms. Afterward, the NOR and CON groups were given 1 ml saline orally every day until the end of the experiment; the PHE and PRO groups were given phenolphthalein or M15 suspension in 1 ml orally, respectively. Compared with the CON group, the fecal water content and intestinal peristalsis improved in the PRO group. Here, intake of M15 effectively attenuated sucralfate-induced constipation, recuperated colonic epithelial integrity, and increased serum levels of gastrointestinal excitatory neurotransmitters (motilin, gastrin, substance P). Analysis of the intestinal microbiota of mice by 16S rRNA metagenomic revealed an increase in the relative abundance of Bacteroides and a decrease in Sclerotinia, Verrucosa and Proteus in the PRO group. Compared with the CON group, the constipation-induced intestinal microecological changes were partially recovered in the PHE and PRO groups. These results demonstrate that M15 enhanced gastrointestinal transit and alleviated in mice with sucralfate-induced constipation.

CAS / MDL: 67-56-1
研究领域: 胃肠病学 · 微生物学 · 药理学
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Acta Biomaterialia · 2025 · IF 9.6

Dual-mechanism mucoadhesive hydrogel integrating pH-independent barriers and autophagy-driven immunotherapy for the treatment of ulcerative colitis

Jie Wang,Shenyuan Ouyang,Gaolong Lin,Dingwei Li,Bingyu Ding,Yumo Chen,Bingjie Tong,Ting Ouyang,Helin Xu,Wenzhi Wu

Current therapies for ulcerative colitis (UC) face critical challenges, including systemic toxicity and inadequate mucosal regeneration. Herein, we present a pioneering dual-mechanism therapeutic platform integrating pH-independent acid-treated sucralfate (ASF) with autophagy-inducing spermidine (Spd) to synergistically address UC pathogenesis. Unlike conventional pH-dependent barrier therapies, ASF forms a mechanically tunable, injectable hydrogel that adheres robustly to colonic mucosa regardless of local pH. Spermidine was easily mounted into ASF hydrogel matrix via electrostatic interaction, with more than 90 % encapsulation efficiency. Moreover, the mechanical strength of ASF hydrogel was precisely modulated by adjusting spermidine amount in formula, making it suitable for effective gut mucosa coverage. Importantly, in vitro permeability test showed that spermidine-loaded ASF hydrogel (Spd-ASF) demonstrated the selective barrier functionality, blocking > 80 % of Escherichia coli and LPS penetration while allowing nutrient permeability. Moreover, micro-CT images demonstrated that rectally infused Spd-ASF hydrogel was uniformly adhered to the colon wall at least for 8 h. In DSS-induced colitis mice, rectally administrating Spd-ASF hydrogel uniquely restored colon length to near-normal levels ( vs. 30 % shortening in controls), reduced proinflammatory cytokines (TNF-α, IL-6, IL-1β) by 60–75 %, and doubled goblet cell density. Mechanistically, Spd-ASF reprogrammed macrophage behavior by activating autophagy and enhancing efferocytosis, driving M2 polarization to resolve inflammation. Notably, Spd-ASF uniquely reversed dysbiosis, elevating beneficial Lactobacillus while suppressing colitis-associated Muribaculaceae and Clostridia . This study is the first to combine mucoadhesive biomaterial engineering with autophagy-mediated immunomodulation, offering a paradigm shift in UC therapy by simultaneously shielding the mucosa and reprogramming inflammatory pathways. Statement of significance Here, autophagy-inducing spermidine (Spd) and pH-independent acid-treated sucralfate (ASF) were combined to create the novel dual-mechanism hydrogel (Spd-ASF), which works in concert to combat UC pathogenesis. The selective barrier functioning of Spd-ASF hydrogel was established by its capacity to permit nutritional permeability while preventing the transfer of toxins (LPS) and pathogenic bacteria ( E. coli ). Additionally, rectally infused Spd-ASF hydrogel was consistently attached on the colon wall for at least eight hours, as seen by micro-CT images. Spd-ASF therapy doubled the density of goblet cells, decreased proinflammatory cytokines (TNF-α, IL-6, and IL-1β) by 60–75 %, boosted helpful Lactobacillus , and lowered pathogenic Muribaculaceae and Clostridia . It also restored colon length in DSS-induced colitis animals. Spd-ASF's therapeutic action was closely linked to promoting cellular efferocytosis and triggering macrophage autophagy.

CAS / MDL: 124-20-9
研究领域: 生物医学工程 · 免疫学 · 胃肠病学 · 药物递送系统 · 生物材料 · 炎症性肠病(IBD)
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