CARBOHYDRATE POLYMERS
·
2021
·
IF 9.381
Xin Li,Mengli Yu,Zhuo Zhu,Chao Lu,Meng Jin,Yuefeng Rao,Qingwei Zhao,Xiaoyang Lu,Chaohui Yu
The anti-tumor necrosis factor-α (anti-TNF-α) blocker, has shown great efficacy for the treatment of inflammatory bowel disease (IBD). However, systemic exposure to it can cause considerable safety problems due to reduced suppression of the systemic immune response and loss of response to the production of anti-drug antibodies. Thus, we try to devise a targeted vehicle system for oral administration of anti-TNF-α antibodies for the treatment of IBD. In the present study, we developed an oral Infliximab (IFX) loaded nano-in-microparticles, based on chitosan (CS)/carboxymethyl chitosan (CMC) and alginate (Alg), which could protect IFX from the harsh environment of the gastrointestinal tract and produce targeted drug delivery to the inflamed intestine . In vivo studies demonstrated that the IFX loaded nano-in-micro vehicle can alleviate colitis by ameliorating inflammation and maintaining the intestinal epithelial barrier.
研究领域:
药学
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胃肠病学
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纳米技术
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药物递送系统
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产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2024
·
IF 10
Yanwei Lv,Mengni Jiang,Yongliang Ouyang,Xiaoyi Zheng,Liang Zhang,Jinpeng Yao,Lianghao Hu,Jiulong Zhao,Zhaoshen Li,Shige Wang
Intestinal barrier dysfunction is related to diseases such as inflammatory bowel disease (IBD) and severe acute pancreatitis (SAP). Butyrate and its derivatives (e.g., sodium butyrate (SB)) can alleviate gut inflammatory responses. Nevertheless, these substances usually cannot fully exert protective effects due to low bioavailability. This research aimed to offer microspheres for treating intestinal barrier injury. Sodium alginate solution is prepared to dissolve SB, followed by mixing with chitosan (CS)-protocatechuic aldehyde (PA)/calcium chloride solution. The required CS-PA/calcium alginate/SB (CPC/SB) microspheres are formed in this manner. Subsequently, the therapeutic effects of CPC/SB microspheres on intestinal barrier injury through in vivo dextran sulfate sodium salt (DSS)-induced IBD and sodium taurocholate (STC)-induced SAP models is explored. Results: The CPC/SB microspheres exhibited excellent antioxidant properties. In vivo bioluminescence imaging experiment confirmed the microspheres effectively targeted the inflammatory gut in IBD. Further in vivo experimental results indicated the microspheres significantly repaired intestinal barrier damage, exerting protective effects in IBD and SAP. Additionally, 16S rDNA sequencing explained the microspheres can regulate the balance between harmful and beneficial bacteria (such as Alistipes, Odoribacter, and Rikenellaceae RC9). This study provides a possible synthetic strategy of microsphere carriers to serve as a potential therapeutic tool for intestinal barrier injury.
研究领域:
药学
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胃肠病学
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生物技术
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分子生物学
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产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2024
·
IF 15.8
Wen Li,Yichen Liu,Xiaoming Zheng,Jing Han,Anchen Shi,Chi Chun Wong,Ruochen Wang,Xunan Jing,Yan Li,Shu Fan,Cuiyu Zhang,Yinnan Chen,Gang Guo,Jun Yu,Junjun She
Intestinal dysbiosis and the associated l-tryptophan metabolic disorder are pivotal in inflammatory bowel disease progression, leading to a compromised intestinal barrier integrity. Remedying the dysfunction in tryptophan metabolism has emerged as a promising therapeutic strategy. Herein, we reprogram the tryptophan metabolism in situ by EcN-TRP@A/G, encapsulating the engineered probiotic, EcN-TRP, with enhanced tryptophan synthesis capacity, for sustained modulation, thereby restoring intestinal barrier function and microbial homeostasis. The pH-responsive dual-layered EcN-TRP@A/G microcapsule developed via high-voltage electrospraying and liquid interface self-assembly, preserved probiotic viability in the harsh gastrointestinal milieu, and facilitated targeted colon release. Bioluminescent tracking in mice reveals a 22.84-fold increase in EcN-TRP@A/G viability and distribution compared to naked EcN-TRP. Targeted metabolomics highlights EcN-TRP@A/G’s modulation of the tryptophan–indole pathway. Oral administration of EcN-TRP@A/G sustained elevates indole metabolites, particularly indole-3-acetic acid and indole-3-propionic acid, in colon tissue for up to 7 days. In IBD mice, EcN-TRP@A/G improves intestinal permeability, reduces inflammation, and recovers the gut microbiome by enhancing beneficial bacteria abundance like Prevotellaceae_UCG-001 and Anaerostipes while suppressing pathogenic strains like Escherichia–Shigella. Our findings offer a cost-effective approach, harnessing the probiotic metabolic potential in situ through engineered modifications for effective IBD treatment.
研究领域:
胃肠病学
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微生物学
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药学
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生物技术
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DOI
PubMed
高影响因子
Science Advances
·
2024
·Vol. 10
·期 30
·
IF 11.7
Guangshuai Zhang,Dandan Song,Ruilong Ma,Mo Li,Bingyang Liu,Zhonggui He,Qiang Fu
The artificial mucus layer, such as hydrogels, used to repair the damaged intestinal barrier, is a promising treatment for inflammatory bowel disease (IBD). However, the currently reported hydrogel-based artificial barriers are administered via rectal injection, causing unnecessary discomfort to patients. Herein, we report an oral hydrogel precursor solution based on thiol-modified hyaluronic acid (HASH). Owing to the reactive oxygen species (ROS)–responsive gelling behavior, our precursor solution formed an artificial mucus coating over the inflamed regions of the intestines, blocking microbial invasion and reducing abnormally activated immune responses. Notably, HASH also modulated the gut microbiota, including increasing the diversity and enhancing the abundance of short-chain fatty acid–associated bacteria, which play a key role in gut homeostasis. We believe that the ROS-responsive artificial mucus layer is a promising strategy for the oral treatment of IBD.
研究领域:
药学
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生物医学工程
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胃肠病学
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产品关联
DOI
PubMed
高影响因子
Drug Design Development and Therapy
·
2024
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IF 4.7
Qi Wu,Kexin Liu,Ruijuan Hou,Xingxing Wu,Xiaoyu Ruan,Mao Wang,Zhiting Sun,Lingchang Meng,Guoliang Dai,Changyin Li,Jing Wu,Genglin Mu
Purpose Inflammatory bowel disease (IBD) is a serious disease that affects the metabolism and inflammatory responses of human beings. From the perspective of traditional Chinese medicine, damp-heat syndrome is one of the main syndromes of IBD. Rhizoma Paridis, also known as the root of Paris polyphylla, a well-known herbal medicine used in China, is used to treat IBD with damp-heat syndrome (IBD-DH). However, uncertainty still exists regarding the underlying mechanisms and the impact of Rhizoma Paridis on IBD-DH.Methods The rats in the model (DAT) and medication administration (Rhizoma Paridis total saponins (RPTS) and Pennogenin (PN)) groups were given a high temperature and high humidity environment, high fat and high sugar diet combined with 2,4,6-trinitrobenzene sulfonic acid (TNBS) to establish the model of experimental colitis of damp-heat type, and the normal control group (RNC) rats were given a normal diet at normal temperature and humidity. Damp-heat control group (DNC) was set with the same condition as DAT without TNBS. Hematoxylin-Eosin (HE) staining was used to observe the histopathological morphology of the rat colorectum. The expression of the metabolism-related genes (Phospholipase A2 (sPLA2, cPLA2), and phosphatidylethanolamine N-methyltransferase (PEMT)) was assessed by using real-time quantitative PCR analysis (RT–qPCR). And the levels of the metabolism-related proteins (sPLA2, cPLA2), S100A8/9, Arg-1, and cytokines were detected by enzyme-linked immunosorbent assay (ELISA) kit. To investigate lipids and amino acids which closely associated with the IBD and IBD-DH, lipid pseudotargeted metabolomics with UHPLC-TQ/MS analysis method, as well as targeted quantitative amino acid analysis were performed.Results Our data showed that RPTS (50 mg/kg) and PN (20 mg/kg) significantly ameliorated the severity of TNBS-induced colitis and downregulated the levels of circulating proinflammatory cytokines. Compared with RNC group, lipid pseudotargeted metabolomics demonstrated that glycerophospholipids, sphingolipids, carnitine, and glycerolipids were the four most perturbed lipid classes, and amino acids targeted metabolomics demonstrated that serine, N-acetylneuraminic acid, histidine, proline, taurine, and kynurenine changed significantly in DAT group . Correlation analyses showed tight associations between most of differential metabolites and proinflammatory cytokines. RPTS and PN both regulated glycerophospholipid metabolism and sphingolipid metabolism. However, both of them did not have a significant effect on amino acid modulation. RPTS and PN potentially regulated sPLA2, cPLA2, and PEMT.Conclusion These results showed that RPTS (50 mg/kg) and PN (20 mg/kg) effectively alleviated rats’ colitis of damp-heat type, affected cytokines, and altered lipid metabolism without significant modulation on amino acid metabolism.
研究领域:
中医
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药理学
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代谢组学
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炎症
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胃肠病学
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产品关联
DOI
PubMed
高影响因子
Pharmaceutics
·
2024
·Vol. 16
·期 10
·1243
·
IF 4.9
Yiqiong Xie,Ying Ma,Lu Xu,Hongwen Liu,Weihong Ge,Baojuan Wu,Hongjue Duan,Hongmei Zhang,Yuping Fu,Hang Xu,Yuxiang Sun,Zhou Han,Yun Zhu
Background: Inflammatory bowel disease (IBD), characterized by chronic inflammation of the digestive tract, involves angiogenesis as a key pathogenic mechanism. Ginsenoside Rg3, derived from the traditional Chinese herb ginseng, is recognized for its anti-angiogenic properties but is limited by low oral bioavailability. This necessitates the development of an alternative delivery system to improve its therapeutic effectiveness.Methods: Pluronic F-127 (F127) and Pluronic F-68 (F68) were used to construct Rg3-loaded thermosensitive hydrogel Gel-Rg3. Meanwhile, a series of physicochemical properties were determined. Then the safety and pharmacological activity of Gel-Rg3 were evaluated in vitro and in vivo using human umbilical vein endothelial cells (HUVECs) and colitis mouse model, in order to initially validate the potential of Gel-Rg3 for the treatment of IBD.Results: We engineered a rectally administrable, thermosensitive Gel-Rg3 hydrogel using F127 and F68, which forms at body temperature, enhancing Rg3’s intestinal retention and slowly releasing the drug. In vitro, Gel-Rg3 demonstrated superior anti-angiogenic activity by inhibiting HUVEC proliferation, migration, and tube formation. It also proved safer and better suited for IBD’s delicate intestinal environment than unformulated Rg3. In vivo assessments confirmed increased intestinal adhesion and anti-angiogenic efficacy.Conclusions: The Gel-Rg3 hydrogel shows promise for IBD therapy by effectively inhibiting angiogenesis via rectal delivery, overcoming Rg3’s bioavailability limitations with improved safety and efficacy. This study provides new inspiration and data support for the design of treatment strategies for IBD.
研究领域:
药学
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药理学
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生物医学工程
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炎症研究
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产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2025
·
IF 8.2
Huan Yang,Xu Zhang,Jianshuang Wu,Yao Xiao,Liangliang Dai,Gaoyang Wang,Xiaohong Zhang,Chenghu Hu,Shuixiang He,Zhang Yuan
Inflammatory bowel disease (IBD) is a complex chronic intestinal disorder in which excessive oxidative stress, dysregulated immune response, and microbiota dysbiosis contribute to recurrent episodes of inflammation in the colonic mucosa. Current clinical treatments focusing solely on inflammation resolution often exhibit limited efficacy due to the inability to fundamentally improve the pathological microenvironment. Herein, a probiotic membrane-modified drug delivery nanocomposite, namely, MPDA@Cur@EM, is developed for the comprehensive treatment of IBD. It contains two components: the curcumin-loaded mesoporous polydopamine nanoparticle (MPDA@Cur) as the core and the Escherichia coli Nissle 1917 outer membrane (EM) as the surface. For MPDA@Cur, the pathological microenvironment triggers the responsive release of curcumin. Importantly, MPDA@Cur can effectively alleviate the inflammatory response of LPS-activated macrophages through MPDA-mediated ROS scavenging and curcumin-induced M2 polarization. In the dextran sulfate sodium (DSS)-induced colitis model, the EM coating not only allows for the targeting enrichment of orally administered MPDA@Cur@EM to the inflamed colonic mucosa, but also participates in the regulation of intestinal flora. Consequently, MPDA@Cur@EM efficiently attenuates the inflammatory reaction and restores the intestinal barrier functions, demonstrated by the multipronged manner of restoring redox balance, remodeling immune homeostasis, and reshaping the gut microecology. Collectively, this work provides a safe and promising codelivery strategy of probiotic product, antioxidative nanoenzyme, and therapeutic drug for comprehensive management of IBD.
研究领域:
药学
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生物医学工程
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胃肠病学
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免疫学
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微生物学
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产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2024
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IF 9.4
Qingrong Li,Cong Zhang,Mengmei Zhu,Jie shan,Haisheng Qian,Yan Ma,Xianwen Wang
Inflammatory bowel disease (IBD) may arise due to disruption of mucosal barriers as a result of dysregulation of the intestinal flora and excessive oxidative stress. The creation of nanomaterials with only microbiota-regulating effects often leads to inadequate therapeutic outcomes caused by the disruption of a healthy microbial balance and the emergence of tissue harm caused by excessive oxidative stress. This report describes the multifunctional activity of ultrasmall W-GA nanodots, which can precisely regulate the intestinal microbiome by inhibiting the abnormal expansion of Enterobacteriaceae during colitis and alleviating the damage caused by oxidative stress to the reconstructive microflora, ultimately restoring intestinal barrier function. W-GA nanodots have been synthesized through a simple coordination reaction and can be dispersed in various solvents in vitro , demonstrating favorable safety profiles in cells, significant clearance of reactive oxygen and nitrogen species (RONS), and increased cell survival in models of oxidative stress induced by hydrogen peroxide (H 2 O 2 ). Through oral or intravenous administration, the W-GA nanodots were shown to be highly safe when tested in vivo , and they effectively reduced colon damage in mice with DSS-induced colitis by restoring the integrity of the intestinal barrier. W-GA nanodots have enabled the integration of microflora reprogramming and RONS clearance, creating a potent therapeutic strategy for treating gut inflammation. Consequently, the development of W-GA nanodots represents a promising strategy for enhancing the formation and preservation of the intestinal barrier to treat IBDs by suppressing the growth of Enterobacteriaceae , a type of facultative anaerobic bacterium, and facilitating the effective removal of RONS. Ultimately, this leads to the restoration of the intestinal barrier's functionality. Statement of Significance An increasing number of nanoparticles are under development for treating inflammatory bowel disease. Although they can alleviate inflammation symptoms by regulating reactive oxygen and nitrogen species (RONS) and microbiota, their understanding of the mechanism behind microbiota regulation is limited. This study synthesized W-GA nanodots using a straightforward one-pot synthesis method. Simple synthesis holds significant promise for clinical applications, as it encompasses multiple nanoenzyme functions and also exhibits Enterobacteriaceae inhibitory properties.Thus, it contributes to ameliorating the current medical landscape of inflammatory bowel disease.
研究领域:
纳米技术
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胃肠病学
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药学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Bioactive Materials
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2022
·
IF 16.874
Qijiang Mao,Haoqi Pan,Yiyin Zhang,Yi Zhang,Qiuwen Zhu,Yi Hong,Zhengze Huang,Yang Li,Xu Feng,Yifeng Fang,WenChao Chen,Pengfei Chen,Bo Shen,Hongwei Ouyang,Yuelong Liang
Inflammatory bowel disease (IBD) is a chronic, immune-mediated inflammatory disease characterized by the destruction of the structure and function of the intestinal epithelial barrier. Due to the poor remission effect and severe adverse events associated with current clinical medications, IBD remains an incurable disease. Here, we demonstrated a novel treatment strategy with high safety and effective inflammation remission via tissue-adhesive molecular coating. The molecular coating is composed of o-nitrobenzaldehyde (NB)-modified Gelatin (GelNB), which can strongly bond with –NH 2 on the intestinal surface of tissue to form a thin biophysical barrier. We found that this molecular coating was able to stay on the surface of the intestine for long periods of time, effectively protecting the damaged intestinal epithelium from irritations of external intestinal metabolites and harmful flora. In addition, our results showed that this coating not only provided a beneficial environment for cell migration and proliferation to promote intestinal repair and regeneration, but also achieved a better outcome of IBD by reducing intestinal inflammation. Moreover, the in vivo experiments showed that the GelNB was better than the classic clinical medication—mesalazine. Therefore, our molecular coating showed potential as a promising strategy for the prevention and treatment of IBD.
研究领域:
药理学
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生物医学工程
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胃肠病学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ADVANCED MATERIALS
·
2025
·
IF 26.8
Xiaoya Ding,Jiante Li,Luoran Shang,Yuanjin Zhao
The use of micromotors-based delivery systems for inflammatory bowel disease (IBD) treatment has recently gained considerable interest. The current research primarily focuses on how to design micromotors with more elaborate geometries and actuation mechanisms to improve IBD therapeutic effects. Herein, a novel type of reactive oxygen species (ROS)-responsive hemispheroid adhesive micromotors (HMPs) as efficient delivery systems is developed to treat IBD. Such HMPs are fabricated through microfluidic electrospray technique, with a platinum (Pt) layer and dopamine (DOPA) coating layer covered on its top surface and baseplate, respectively. The Pt on HMPs′ top surface can produce oxygen from hydrogen peroxide, thereby providing a propulsion force for them to move spontaneously upon exposure to ROS environment. Moreover, the DOPA layer on the baseplate contributed to the outstanding adhesive capacity to tissues. Therefore, by incorporating anti-inflammatory dexamethasone (DXM) into HMPs, the resultant micromotor systems are imparted with superior antioxidant and anti-inflammatory capacities, which also exhibits desirable therapeutic effect upon treating IBD by alleviating inflammatory response, restoring epithelial barrier functions, and mitigating IBD-associated symptoms. The treatment mechanism of DXM-loaded HMPs mainly involves alleviating oxidative stress, reducing proinflammatory cytokines secretion, and protecting intestinal barrier. Collectively, these results illustrate HMPs-based micromotor systems are valuable for gastrointestinal disease treatment.
研究领域:
生物医学工程
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药物递送系统
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纳米医学
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胃肠病学
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微型机器人
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2021
·Vol. 10
·期 23
·2101618
·
IF 9.933
Ning Zhao,Fei-Er Yang,Cong-Ying Zhao,Shi-Wen Lv,Jin Wang,Jing-Min Liu,Shuo Wang
It is of great significance to eliminate excessive reactive oxygen species (ROS) for treating inflammatory bowel disease (IBD). Herein, for the first time, a novel nanozyme NiCo 2 O 4 @PVP is constructed via a step-by-step strategy. Noticeably, the existence of oxygen vacancy in the NiCo 2 O 4 @PVP is helpful for capturing oxygenated compounds, while both redox couples of Co 3+ /Co 2+ and Ni 3+ /Ni 2+ will offer richer catalytic sites. As expected, the obtained NiCo 2 O 4 @PVP exhibits pH-dependent multiple mimic enzymatic activities. Benefiting from the introduction of polyvinylpyrrolidone (PVP), the NiCo 2 O 4 @PVP possesses good physiological stability and excellent biosafety in stomach and intestines’ environment. Meanwhile, the NiCo 2 O 4 @PVP also presents strong scavenging activities to ROS in vitro, including • O 2 − , H 2 O 2 , as well as • OH. Furthermore, a dextran sodium sulfate (DSS)-induced colitis model is established for evaluating the anti-inflammatory activity of NiCo 2 O 4 @PVP in vivo. Based on the size-mediated and charge-mediated mechanisms, the nanozyme can pass through the digestive tract and target the inflamed site for oral-administrated anti-inflammatory therapy. More interestingly, compared with the model group, the expression levels of inflammatory factors (e.g., Interleukin- 6 (IL-6), Interleukin- 1β (IL-1 β) , tumor necrosis factor-α (TNF- α ), and inducible nitric oxide synthase (iNOS)) in colon of mice show a significant decrease after nanozyme intervention, thereby inhibiting the development of IBD. In short, current work provides an alternative therapy for patients suffering from IBD.
研究领域:
纳米技术
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生物医学工程
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药学
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炎症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2024
·
IF 4.8
Fang Shi,Yong-Sheng Gao,Shu-Mei Han,Cheng-Suo Huang,Qing-Sheng Hou,Xiao-wen Wen,Ben-Shi Wang,Zhen-Yu Zhu,Lei Zou
Metabolic changes have been linked to the development of inflammatory bowel disease (IBD), which includes colitis. Allulose, an endogenous bioactive monosaccharide, is vital to the synthesis of numerous compounds and metabolic processes within living organisms. Nevertheless, the precise biochemical mechanism by which allulose inhibits colitis remains unknown. Allulose is an essential and intrinsic protector of the intestinal mucosal barrier, as it maintains the integrity of tight junctions in the intestines, according to the current research. It is also important to know that there is a link between the severity of inflammatory bowel disease (IBD) and colorectal cancer (CRC), chemically-induced colitis in rodents, and lower levels of allulose in the blood. Mice with colitis, either caused by dextran sodium sulphate (DSS) or naturally occurring colitis in IL-10 -/- mice, had less damage to their intestinal mucosa after being given allulose. Giving allulose to a colitis model starts a chain of reactions because it stops cathepsin B from ejecting and helps lysosomes stick together. This system effectively stops the activity of myosin light chain kinase (MLCK) when intestinal epithelial damage happens. This stops the breakdown of tight junction integrity and the start of mitochondrial dysfunction. To summarise, the study's findings have presented data that supports the advantageous impact of allulose in reducing the advancement of colitis. Its ability to stop the disruption of the intestinal barrier enables this. Therefore, allulose has potential as a medicinal supplement for treating colitis.
研究领域:
胃肠病学
·
药理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）