JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2021
·
IF 5.279
You Wu,Jiaojiao Li,Wenjiao Ding,Zheng Ruan,Li Zhang
The intestinal barrier is essential for maintaining human intestinal health. The growing number of studies has shown that both puerarin and tryptophan and its metabolites have a beneficial effect on the intestinal barrier. This study aims at the combination of puerarin and tryptophan or its metabolites for improving the intestinal barrier. In our study, 40 female Sprague–Dawley rats were randomly divided into five groups (n = 8) for a 4-week experiment and dextran sodium sulfate was used to induce an intestinal barrier injury in rats. Our results showed that puerarin combined with tryptophan or its metabolites (indole-3-propionic acid, IPA) improved the intestinal barrier by enhancing the mucus layer barrier, which was mainly achieved by increasing the number of goblet cells and promoting the secretion of MUC2. Both TRPM5 and VAMP8 promoted MUC2 secretion in goblet cells through exocytosis, but their mechanisms of action are different. In our study, we found that puerarin and tryptophan showed different effects on TRPM5 and VAMP8, respectively. Puerarin enhances the expression of TRPM5, and tryptophan inhibits the expression of TRPM5; however, puerarin and tryptophan have no significant effect on the expression of VAMP8.
研究领域:
药理学
·
胃肠病学
·
营养学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
·
2024
·
IF 3.9
Jiawen Lu,Dan Su,Ying Yang,Mengni Shu,Yuting Wang,Xingtao Zhou,Qiang Yu,Chang Li,Jianhua Xie,Yi Chen
Mycotoxins and thermal processing hazards are common contaminants in various foods and cause severe problems in terms of food safety and health. Combined use of acrylamide (AA) and ochratoxin A (OTA) would result in more significant intestinal toxicity than either toxin alone, but the underlying mechanisms behind this poor outcome remain unclear. Herein, we established the co-culture system of Caco-2/HT29-MTX cells for simulating a real intestinal environment that is more sensitive to AA and OTA, and showed that the combination of AA and OTA could up-regulate permeability of the intestine via increasing LY permeabilization, and decreasing TEER, then induce oxidative stress imbalance (GSH, SOD, MDA, and ROS) and inflammatory system disorder (TNF-α, IL-1β, IL-10, and IL-6), thereby leading a rapid decline in cell viability. Western blot, PAS- and AB-staining revealed that AA and OTA showed a synergistic effect on the intestine mainly through the disruption of tight junctions (TJs) and a mucus layer. Furthermore, based on correlation analysis, oxidative stress was more relevant to the mucus layer and TJs. Therefore, our findings provide a better evaluation model and a potential mechanism for further determining or preventing the combined toxicity caused by AA and OTA.
研究领域:
食品安全
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毒理学
·
细胞生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2025
·
IF 16
Zhi-Hao Wang,Xuejiao Zeng,Shuhao Zhang,Hailong Li,Jianchao Zhou,Yefei Yang,Wanting Huang,Fengqin Zhao,Zhongyang Liu,Junjie Liu,Yurong Hu,Jinjin Shi
Oral administration is a traditional, safe, and widely used drug delivery strategy. However, the delivery efficiency of the oral drug delivery system is hindered by the long gastrointestinal tract, filled with dense and viscous mucus. Herein, we presented an acoustic-magnetic responsive nanomotor (MMSNP) for oral drug delivery via gastrointestinal site navigation and mucus layer penetration. MMSNP has a Janus rod-shaped structure composed of iron tetroxide and mesoporous silica, which could be guided to various intestinal segments with an external magnetic field based on the demand of different diseases. In addition, the rod-like system could effectively penetrate the dense and viscous mucus under ultrasound radiation to improve the bioavailability of loaded drugs. In diabetes rats, small intestinal navigation and mucus penetration of the nanomotor increased the oral relative bioavailability of metformin (Met) by 78.0% and the effective hypoglycemic time by 1.1-fold than pure Met. In orthotopic colorectal cancer (CRC)-bearing mice, magnetically mediated colorectal navigation increased the anchoring efficiency of nanomotors by 4.2-fold, and ultrasound propulsion increased the mucus penetration efficiency of MMSNP by 5.2-fold, leading to a vastly improved delivery efficiency of cisplatin (CP) and a superior tumor inhibition rate of 97.2%. This simple and versatile nanomotor has broad application prospects in the treatment of gastrointestinal diseases, providing a promising and universal strategy for clinical conversion of orally administered drugs.
研究领域:
生物医学工程
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药剂学
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纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2021
·Vol. 19
·期 1
·1-21
·
IF 10.435
Guo Shiqi,Liang Yanzi,Liu Lanze,Yin Miaomiao,Wang Aiping,Sun Kaoxiang,Li Youxin,Shi Yanan
Background The use of drug nanocarriers to encapsulate drugs for oral administration may become an important strategy in addressing the challenging oral absorption of some drugs. In this study—with the premise of controlling single variables—we prepared model nanoparticles with different particle sizes, surface charges, and surface hydrophobicity/hydrophilicity. The two key stages of intestinal nanoparticles (NPs) absorption—the intestinal mucus layer penetration stage and the trans-intestinal epithelial cell stage—were decoupled and analyzed. The intestinal absorption of each group of model NPs was then investigated.Results Differences in the behavioral trends of NPs in each stage of intestinal absorption were found to result from differences in particle properties. Small size, low-magnitude negative charge, and moderate hydrophilicity helped NPs pass through the small intestinal mucus layer more easily. Once through the mucus layer, an appropriate size, positive surface charge, and hydrophobic properties helped NPs complete the process of transintestinal epithelial cell transport.Conclusion sTo achieve high drug bioavailability, the basic properties of the delivery system must be suitable for overcoming the physiological barrier of the gastrointestinal tract.
研究领域:
药学
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纳米技术
·
生物药剂学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2020
·
IF 7.727
Yuanna Shen,Yiqing Zou,Xiaonan Chen,Pengyu Li,Yiqin Rao,Xuan Yang,Yingying Sun,Haiyan Hu
The prevalence of infections with Helicobacter pylori ( H. pylori ) has progressively increased worldwide, which demonstrated to be closely correlated to its biofilm formation. H. pylori biofilms protect the bacteria by significantly decreasing their sensitivity to antibiotics. Moreover, H. pylori colonizes on the gastrointestinal tract epithelium which is covered by mucus layer, acting as another barrier to prevent antibacterial agents from reaching the colonization sites. Herein, we prepared four types of versatile self-assembled nanodrugs (BD/RHL NDs) containing lipophilic alkyl berberine derivatives (BDs) and rhamnolipids (RHL) to overcome the dual obstructions of both mucus layer and biofilms. Molecular dynamics simulations estimated that the driving forces for self-assembly of BD/RHL NDs were electrostatic and hydrophobic interactions. BD/RHL NDs, characterized by appropriate size, negative charge and enhanced hydrophilicity, successfully penetrated through mucus layer without interacting with mucins. In in vitro experiments, BD/RHL NDs exhibited substantial ability to eradicate H. pylori biofilms by destroying their extracellular polymeric substances (EPS) and killing planktonic H. pylori . Furthermore, BD/RHL NDs inhibited the adherence of H. pylori on both biotic and abiotic surfaces, therefore cut off the critical step of the biofilm re-formation which was associated with the recrudescence of infections. In an H. pylori- infected mice model, C10-BD/RHL NDs group showed 40 folds less remnant H. pylori and greater mucosal protection compared with the conventional clinical triple therapy. In conclusion, BD/RHL NDs could penetrate through mucus layer and effectively eradicate H. pylori biofilms in vitro and in vivo , providing a novel strategy for clinical treatment of biofilm-related infections.
研究领域:
药学
·
微生物学
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纳米技术
·
传染病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2021
·
IF 9.229
Yi Zhang,Mengting Xiong,Xiaomin Ni,Jingrou Wang,Hehui Rong,Yuqing Su,Shihui Yu,Imran Shair Mohammad,Sharon Shui Yee Leung,Haiyan Hu
Protein and peptide drugs orally suffer from extremely low bioavailability principally for the complicated gastrointestinal environment along with the difficulty of passing through the mucus layer and the underlying epithelium. In our work, we fabricated mesoporous silica nanoparticles with modification groups (MSN-NH2@COOH/CPP5) that effectively penetrated the mucus layer and passed through the intestinal epithelium by mimicking the virus surface. Naked nanoparticles were prepared with inner pores of 6 nm diameter to allow efficient insulin loading and coated with the cationic cell-penetrating KLPVM peptide and the anionic glutaric anhydride to yield hydrophilic MSN-NH2@COOH/CPP5 with a ζ-potential of −0.49 mV. The apparent permeability coefficient of virus-mimicking nanoparticles was 14.61 × 10–5 cm/s. The virus-mimicking nanoparticles showed dramatically lower binding to mucin and faster penetration of the mucus layer than positively charged nanoparticles (MSN@NH2) with a ζ-potential of +35.00 mV. The KLPVM peptide enhanced the uptake of MSN-NH2@COOH/CPP5 by coculturing Caco-2 and E12 cells as an intestinal epithelium model. MSN-NH2@COOH/CPP5 enhanced apical-to-basal transcytosis for being internalized primarily through caveolae-mediated endocytosis. Indeed, for MSN-NH2@COOH/CPP5, the transepithelial transport of the Caco-2 cell monolayer was 2.4-fold higher than MSN@NH2 and 2.0-fold higher than MSN-NH2@COOH. In vitro, loading insulin into nanoparticles maintained the bioactivity of the protein under simulated intestinal conditions. Insulin loaded into MSN-NH2@COOH/CPP5 reduced the diabetic rats’ blood glucose level by nearly 50%. The bioavailability of insulin encapsulated in the MSN-NH2@COOH/CPP5 nanoparticles was 2.1-fold more than insulin when administered directly into the jejunum. Nanoparticles with modifications indicated no significant toxicity in in vitro or in vivo preliminary studies. The obstacles of the mucus layer and intestinal epithelium may be effectively conquered by these virus-mimicking nanoparticles for oral delivery of protein and peptide drugs.
研究领域:
药学
·
纳米技术
·
药物递送系统
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2024
·
IF 15.8
Dan Yuan,Zhicheng Niu,Wenyu Zheng,Qiangzhong Zhao,Feibai Zhou,Mouming Zhao
Overcoming intestinal epithelial barriers to enhance bioavailability is a major challenge for oral delivery systems. Desirable nanocarriers should simultaneously exhibit rapid mucus penetration and efficient epithelial uptake; however, they two generally require contradictory structural properties. Herein, we proposed a strategy to construct multiperformance nanoparticles by modifying the rigidity of amphiphilic nanostructures originating from soy polypeptides (SPNPs), where its ability to overcome multibarriers was examined from both in vitro and in vivo, using curcumin (CUR) as a model cargo. Low-rigidity SPNPs showed higher affinity to mucin and were prone to getting stuck in the mucus layer. When they reached epithelial cells, they tended to be endocytosed through the clathrin and macropinocytosis pathways and further transferred to lysosomes, showing severe degradation and lower transport of CUR. Increased particle rigidity generally improved the absorption of CUR, with medium-rigidity SPNPs bloomed maximum plasma concentration of CUR by 80.62-fold and showed the highest oral bioavailability. Results from monocultured and cocultured cell models demonstrated that medium-rigidity SPNPs were least influenced by the mucus layer and changes in rigidity significantly influenced the endocytosis and intracellular fate of SPNPs. Those with higher rigidity preferred to be endocytosed via a caveolae-mediated pathway and trafficked to the ER and Golgi, facilitating their whole transcytosis, and avoiding intracellular metabolism. Moreover, rigidity modulation efficiently induces the reversible opening of intercellular tight junctions, which synergistically improves the transport of CUR into blood circulation. This study suggested that rigidity regulation on food originated amphiphilic peptides could overcome multiple physiological barriers, showing great potential as natural building block toward oral delivery.
研究领域:
药剂学
·
纳米技术
·
药物递送系统
·
生物物理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Pharmaceutica Sinica B
·
2022
·
IF 14.903
Xiaonan Chen,Yiqing Zou,Shuqi Zhang,Pengchao Fang,Shuxuan Li,Pengyu Li,Yingying Sun,Gang Yuan,Haiyan Hu
Helicobacter pylori ( H. pylori ), creating a global infection rate over 50%, presents great challenges in clinical therapies due to its complex pathological microenvironment in vivo . To improve the eradication efficacy, herein we fabricated a pharmaceutical vesicle RHL/Cl-Ch-cal where cholesterol-PEG, calcitriol and first-line antibiotic clarithromycin were co-loaded in the rhamnolipid-composed outer lipid layer. RHL/Cl-Ch-cal could quickly penetrate through gastric mucus layer to reach H. pylori infection sites, and then effectively destroyed the architecture of H. pylori biofilms, killed dispersed H. pylori and inhibited the re-adhesion of residual bacteria (called biofilms eradication tetralogy). Moreover, RHL/Cl-Ch-cal activated the host immune response to H. pylori by replenishing cholesterol to repair lipid raft on the cell membrane of host epithelial cells. Finally, RHL/Cl-Ch-cal killed the intracellular H. pylori through recovering the lysosomal acidification and assisting degradation. In experiments, RHL/Cl-Ch-cal demonstrated prominent anti- H. pylori efficacy in the classical H. pylori -infected mice model. Therefore, the study provides a “comprehensive attack” strategy for anti- H. pylori therapies including biofilms eradication tetralogy, immune activation and intracellular bacteria killing.
研究领域:
药学
·
微生物学
·
免疫学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2024
·
IF 15.8
Shiyuan Hua,Huiqun Hu,Jin Liu,Feng Lu,Runchang Yu,Xuening Zhang,Haimeng Sun,Ziwei Wang,Yige Li,Jingyan Xia,Feng Xu,Min Zhou
Bacterial pneumonia is one of the most challenging global infectious diseases with high morbidity and mortality. Considering the antibiotic abuse and resistance of bacterial biofilms, a variety of metal-based materials have been developed. However, due to the high oxygen environment of the lungs, some aerobic infection bacteria have high tolerance to oxygen and ROS, and most of the metal-based materials based on ROS may not achieve good therapeutic effects. Inspired by the sensitivity of cuproptosis to aerobic respiratory cells, we designed a copper composite antibacterial nanoparticle and found that it can effectively induce cuproptosis-like death in the aerobic bacteria of the lungs. To address the challenge of in vivo application of cuproptosis, manganese dioxide was first incorporated to deplete protective glutathione, which can interact with copper and thus hinder the interaction of copper with proteins and assist in antibacterial action through immune enhancement. Cuproptosis-like death also requires a large number of copper ions. To meet this demand, we deliver positively hydrophilic modified composite nanoparticles that effectively penetrate the lung mucus layer directly to the lungs through local administration, and the copper ions are further released rapidly by the acidic environment at the infected site, which can further destroy bacterial biofilms in synergy with manganese. This drug-delivery system can effectively treat pneumonia caused by aerobic bacteria and avoid systemic toxicity that can be caused by large doses of copper.
研究领域:
药学
·
纳米技术
·
传染病学
·
材料科学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Drug Delivery and Translational Research
·
2023
·
IF 5.4
Fang Ruiyue,Zhao Ying,Lin Shiyuan,Wei Yue,Chen Hui
This study aimed to enhance the oral absorption of Panax notoginseng saponins (PNS) via nanoparticles modified with thiolated trimethyl chitosan (TMC-Cys) and wheat germ agglutinin (WGA), termed PP-WT NPs. In vitro investigations revealed that PP-WT NPs exhibited delayed release of PNS and a strong tolerance to the gastric acids and digestive enzymes. Moreover, PP-WT NPs exhibited efficient cellular uptake and transport capabilities in the Caco-2/HT29-co-cultured cell model. In vivo animal experiments demonstrated that PP-WT NPs effectively overcame the mucus layer barrier, with the effective permeability coefficients of R1, Rg1, and Rb1 in the small intestine being 1.68, 1.64, and 1.63 times higher than those of free PNS, respectively. Taken together, thiolated trimethyl chitosan and wheat germ agglutinin–modified nanoparticles hold significant potential for improving the oral absorption of PNS, representing an attractive strategy for enhanced therapeutic efficacy.
研究领域:
药学
·
纳米技术
·
药物递送系统
·
药理学
✓ 已验证
产品关联
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
·
生物医学工程
·
胃肠病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2024
·
IF 15.8
Yujie Zhang,Ya Wang,Xiaojiang Zhang,Pengqian Wang,Feiyu Shi,Zhe Zhang,Ruochen Wang,Daocheng Wu,Junjun She
To realize effective and long-term synergistic therapy of ulcerative colitis (UC) with probiotics, we developed gastrointestinal self-adaptive and nutrient self-sufficient Akkermansia muciniphila (AKK)–gelatin porous microgels (AKK@GPMGs). In AKK@GPMGs, AKK was covered with sequential layers of proanthocyanidins (PAs), mucin (MUC), and phosphatidylcholine (PC) to obtain AKK@PAs-MUC-PC (AKK@PMP), and then encapsulated within the methacrylate-modified gelatin porous microgels. AKK@GPMGs provide sufficient mucus as a nutrition source for AKK and boost resistance to stomach acid by 30.49-fold, and colonization in the intestines is enhanced by 83.46 times. The microgels can be dissociated by matrix metalloproteinase at the inflammatory sites of the intestine, and release AKK@PMP, which acts as “band-aid” that adheres to the inflamed colon for a long time and offers improved synergistic therapy for UC. Compared to uncoated AKK, AKK@GPMGs increase reactive oxygen species scavenging capacity by 26.47 times, improve the intestinal mucus layer thickness by 5.63 times, increase the goblet cells abundance by 3.93 times, reduce intestinal permeability by 5.60 times and significantly enhance beneficial gut microbiota while repressing harmful microbiota. These results indicate that AKK@GPMGs can restore mucus layer and tight junction integrity, reduce inflammation and oxidative stress, and regulate gut microbiota homeostasis to effectively treat intestinal inflammation.
研究领域:
药学
·
生物医学工程
·
胃肠病学
·
微生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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