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ACS Biomaterials Science & Engineering · 2024 · IF 5.4

In Situ Gelation Strategy for Efficient Drug Delivery in a Gastrointestinal System

Yucui Shen,Ye Feng,Shengjie Liang,Chunyong Liang,Baoe Li,Donghui Wang,Jianwei Sun

Developing a microenvironment-responsive drug delivery system (DDS) for the gastrointestinal system is of great interest to enhance drug efficiency and minimize side effects. Unfortunately, the rapid-flowing digestive juice in the gastrointestinal tract and the continuous contraction and peristalsis of the gastrointestinal tract muscle accelerate the elimination of drug carriers. In this study, a boric hydroxyl-modified mesoporous Mg(OH)2 drug carrier is prepared to prolong the drug retention time. Results show that the newly designed DDS presents high biocompatibility and can immediately turn the free polyhydric alcohol molecules into a gelation form. The in situ-formed gelation network presents high viscosity and can prevent the drug carriers from being washed away by the digestive juice in the gastrointestinal tract.

研究领域: 药剂学 · 生物医学工程
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ACS Applied Bio Materials · 2019 · IF 0

Exploring the Interaction of Fullerenol with Key Digestive Proteases Using Raman-Based Frequency-Shift Sensing and Molecular Simulation Analysis

Dan Xie,Ya-Nan Chang,Gengmei Xing,Lina Zhao,Min Li,Yuliang Zhao

Fullerenol has been demonstrated to be a potential anticancer nanodrug thanks to its excellent antioxidant properties. In this work, surface-enhanced Raman scattering (SERS)-based frequency shift method is employed to explore the interaction between fullerenol and the key digestive proteases (pepsin and trypsin) in the gastrointestinal tract. A dynamic adsorption process of fullerenol on pepsin/trypsin has been monitored by our detection platform. The binding sites of fullerenol to trypsin and pepsin are evidenced by introducing their inhibitors to the detection system, and the binding configurations/modes of fullerenol to pepsin and trypsin are precisely determined through computational simulations. The permeability of fullerenol through intestinal epithelial cells monolayer is also investigated and the results show that it can reach 6% in 6 h and 13% in 48 h, indicating its high oral bioavailability in human body. This work demonstrates the activity of fullerenol in the gastrointestinal tract and provides potential guidance for appropriate oral medicine design with the aid of a molecular docking method.

研究领域: 药理学 · 生物化学 · 纳米医学
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JOURNAL OF HAZARDOUS MATERIALS · 2018 · IF 6.434

Influence of gastrointestinal tract on metabolism of bisphenol A as determined by in vitro simulated system

Yonghua Wang,Min Rui,Yang Nie,Guanghua Lu

Oral exposure is a major route of human bisphenol A (BPA) exposure. However, influence of gastrointestinal tract on BPA metabolism is unavailable. In this study, in vitro simulator of the human intestinal microbial ecosystem (SHIME) was applied to investigate the changes in bioaccessibility and metabolism of BPA in different parts of gastrointestinal tract (stomach, small intestine and colon). Then the human hepatoma cell line HepG2 was employed to compare toxic effects of BPA itself and effluents of SHIME system on hepatic gene expression profiles. Results showed that level of bioaccessible BPA decreased with the process of gastrointestinal digestion. But the gastrointestinal digestion could not completely degrade BPA. Then, BPA exposure significantly changed microbial community in colons and increased the percentage of microbes shared in ascending, transverse and descending colons. Abundances of BPA-degradable bacteria, such as Microbacterium and Alcaligenes , were up-regulated. Further, SHIME effluents significantly up-regulated expressions of genes related to estrogenic effect and oxidative stress compared to BPA itself, but reduced or had little change on the risk of cell apoptosis and fatty deposits. This study sheds new lights on influence of gastrointestinal digestion on bioaccessibility and toxic effects of BPA.

CAS / MDL: 80-05-7
研究领域: 毒理学 · 环境科学 · 微生物学 · 分子生物学
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ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH · 2022 ·Vol. 29 ·期 42 ·64244-64251 · IF 5.19

Property of arylsulfatase and β-glucuronidase extracted from digestive tracts of Cipangopaludina chinensis and their cleavage performance on conjugated natural estrogens

Zhao Ke-meng,Liu Ze-hua,Zhang Jun,Zhong Shu-shu,Dang Zhi

Arylsulfatase and β-glucuronidase are the two substantial enzymes having a significant role in the cleavage of conjugated natural estrogens (C-NEs). The present study reports that arylsulfatase and β-glucuronidase have been abundantly found in the digestive tracts of Cipangopaludina chinensis ; in which, their corresponding activities were 60 and 5 U/g wet waste, respectively. The arylsulfatase from Cipangopaludina chinensi s could show high activity at low temperatures. Hence, its activity still remained at 53.2% of maximal activity even at an extremely low temperature of 4 ℃; while the corresponding activities of arylsulfatase from Helix pomatia or activated sludge were less than 20% and 10%, respectively. The arylsulfatase and β-glucuronidase from Cipangopaludina chinensis could efficiently cleave C-NEs suggesting that they could be alternative enzymes derived from Helix pomatia that are used for cleavage of conjugated compounds in environmental or biological sample analysis. Meanwhile, they might also be used to enhance the cleavage of C-NEs in municipal wastewater.

研究领域: 环境生物学 · 生物化学
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ADVANCED MATERIALS · 2024 ·Vol. 36 ·期 40 ·2405290 · IF 27.4

Blue Laser Triggered Hemostatic Peptide Hydrogel for Gastrointestinal Bleeding Treatment

Qiang Luo,Jie Luo,Zhaohui Luan,Kaige Xu,Lixing Tian,Kebin Zhang,Xue Peng,Mengxue Yuan,Chuanhao Zheng,Zhenzhen Shu,Yuchen Zhang,Shali Tan,Ruijue Dan,Kibret Mequanint,Chaoqiang Fan,Malcolm Xing,Shiming Yang

In an emergency, nonvariceal upper gastrointestinal bleeding (NVUGIB), endoscopic hemostasis is considered the gold standard intervention. However, current endoscopic hemostasis is very challenging to manage bleeding in large-diameter or deep lesions highly prone to rebleeding risk. Herein, a novel hemostatic peptide hydrogel (HPH) is reported, consisting of a self-assembly peptide sequence CFLIVIGSIIVPGDGVPGDG (PFV) and gelatin methacryloyl (GelMA), which can be triggered by blue laser endoscopy (BLE) for nonvariceal upper gastrointestinal bleeding treatment without recurring bleeding concerns. Upon contact with GelMA solution, PFV immediately fibrillates into β-sheet nanofiber and solvent-induced self-assembly to form HPH gel. HPH nanofiber networks induced ultrafast coagulation by enveloping blood cells and activating platelets and coagulation factors even to the blood with coagulopathy. Besides its remarkable hemostatic performance in artery and liver injury models, HPH achieves instant bleeding management in porcine NVUGIB models within 60 s by preventing the rebleeding risk. This work demonstrates an extraordinary hemostatic agent for NVUGIB intervention by BLE for the first time, broadening potential application scenarios, including patients with coagulopathy and promising clinical prospects.

CAS / MDL:
研究领域: 生物医学工程 · 材料科学 · 消化内科
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ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY · 2022 · IF 5.785

DEHP triggers a damage severity grade increase in the jejunum in quail (Coturnix japonica) by disturbing nuclear xenobiotic receptors and the Nrf2-mediated defense response

Tian-Ning Yang,Xue-Nan Li,Xiao-Wei Li,Jin-Yang Li,Yue-Qiang Huang,Jin-Long Li

As a plasticizer , di-2-ethylhexyl phthalate (DEHP) has been listed as a potential endocrine disruptor by The World Health Organization. The toxicity of DEHP has been widely studied, but its toxicity on the digestive tract of birds has not been clarified. Female quail were treated by gavage with DEHP (250, 500, 750 mg/kg), with the blank and vehicle control groups reserved. The result showed that DEHP raised the damage severity grade, and decreased the ratio of villus length to crypt depth. The content and activity of cytochrome P450 system (CYP450s) were increased by DEHP. DEHP interfered with the transcription of nuclear xenobiotic receptors (NXRs), CYP isoforms, and the nuclear factor-E2-related factor 2 (Nrf2) signaling pathway. This study revealed DEHP could cause the imbalance in CYP450s mediated by NXRs, and then promote Nrf2 mediated antioxidant defense. This study provided new evidence about the mechanisms of DEHP-induced toxic effects on digestive tract.

CAS / MDL: 117-81-7
研究领域: 毒理学 · 鸟类生物学 · 环境科学 · 分子生物学
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ANALYTICA CHIMICA ACTA · 2023 · IF 6.2

Integrated sample processing and counting microfluidic device for microplastics analysis

Mengmeng Zhang,Xiaoyang Wang,Yajun Zhang,Yiqiang Fan

Background The presence of microplastics is widespread in the ocean, freshwater, soil, or even in the human body. The current microplastics analysis method involves a relatively complicated sieving, digestion filtration, and manual counting process, which is both time-consuming and requires experienced operation personnel. Result This study proposed an integrated microfluidic approach for the quantification of microplastics from river water sediment and biosamples. The proposed two-layer PMMA-based microfluidic device is able to conduct the sample digestion, filtration and counting processes inside the microfluidic chip with the preprogrammed sequence. For demonstration, samples from river water sediment and fish gastrointestinal tract were analyzed, result indicate the proposed microfluidic device is able to perform the quantification of microplastics from river water and biosamples. Significance and novelty Compared with the conventional approach, the proposed microfluidic-based sample processing and quantification method for microplastics are simple, low-cost and with low demand for laboratory equipments, the self-contained system also has the application potential for the continuous on-site inspection of microplastics.

研究领域: 环境科学 · 微流控技术 · 分析化学
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ADVANCED FUNCTIONAL MATERIALS · 2021 ·Vol. 32 ·期 16 ·2109332 · IF 18.808

Adhesive Hemostatic Hydrogel with Ultrafast Gelation Arrests Acute Upper Gastrointestinal Hemorrhage in Pigs

Xianfeng Xia,Xiayi Xu,Bin Wang,Di Zhou,Weili Zhang,Xian Xie,Huasheng Lai,Ju Xue,Aliza Rai,Zhuo Li,Xin Peng,Pengchao Zhao,Liming Bian,Philip Wai-Yan Chiu

Upper gastrointestinal (GI) hemorrhage is a common clinical emergency worldwide. Endoscopic hemostasis is the current first line treatment. Nevertheless, for patients with severe active bleeding and challenging anatomy, endoscopic management can be still difficult and usually requires a higher level of surgical expertise. A simple and effective method of endoscopic hemostasis is therefore in acute clinical demand. Herein a hemostatic hybrid hydrogel comprised of hyaluronic acid and polyethylene glycol stabilized by thiourea–catechol coupling and disulfide bonds is reported. The hybrid hydrogels exhibit enhanced mechanical properties, short gelation time, and good blood clotting ability compared with fibrin gels. The in vivo hemostatic efficacy is confirmed in a rat model of arterial bleeding, in which the rapid gelation of hybrid hydrogels after topical application effectively arrests blood loss with no rebleeding occurring during resuscitation when blood pressure approximately recovers to normal. A large animal study further demonstrates the efficacy of hybrid hydrogels to achieve endoscopic hemostasis against upper GI hemorrhage in pigs. Follow-up observations show that the hybrid hydrogels can remain adherent at the bleeding wound for 48 h, indicating the sustained hemostatic function in vivo. Collectively, this work demonstrates a promising hemostatic hydrogel for endoscopic hemostasis in upper GI hemorrhage.

CAS / MDL: 1122-58-3 7087-68-5
研究领域: 生物材料 · 医学工程 · 临床医学
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ACS Biomaterials Science & Engineering · 2023 · IF 5.8

Bacteria-Loaded Gastro-Retention Oral Delivery System for Alcohol Abuse

Qikun Cheng,Mingzhi Xie,Guowei Li,Wei Xue,Lexiang Zeng,Dong Ma

Alcohol abuse is harmful to human health, and many strategies have been developed to retard this harm through protecting liver or activating relative enzymes. In this study, a new strategy of decreasing the alcohol absorption directly depending on the dealcoholization by the bacteria in the upper gastrointestinal (GI) tract was reported. To realize this, a bacteria-loaded gastro-retention oral delivery system with pore structure was constructed through emulsification/internal gelation, which could relieve acute alcohol intoxication in mice successfully. It was found that this bacteria-loaded system kept the above 30% suspension ratio in the simulated gastric fluid for 4 min, displayed good protection effect for the bacteria, and decreased the alcohol concentration from 50 to 30% below within 24 h in vitro. The in vivo imaging results demonstrated that it remained in the upper GI tract until 24 h and reduced 41.9% alcohol absorption. The mice with oral administration of the bacteria-loaded system were found with normal gait, smooth coat, and less liver damage. Although the intestinal flora distribution was influenced slightly during the oral administration, it could restore to normal levels only one day after stopping oral administration quickly, suggesting good biosafety. In conclusion, these results revealed that the bacteria-loaded gastro-retention oral delivery system might intake alcohol molecules rapidly and has huge potential in the treatment of alcohol abuse.

CAS / MDL: 10043-52-4
研究领域: 药理学 · 生物技术 · 胃肠病学
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AAPS PHARMSCITECH · 2019 ·Vol. 20 ·期 7 ·1-8 · IF 2.608

A Novel Micron-Size Particulate Formulation of Felodipine with Improved Release and Enhanced Oral Bioavailability Fabricated by Coaxial Electrospray

Yin Xuezhi,Pan Hao,Liu Hongfei

The antihypertensive drug felodipine (FD) is a typical biopharmaceutics classification system (BCS) II drug; thus, improving the dissolution rate of FD is very important to enhance its bioavailability. Besides, according to the in situ “close loop” perfusion assay, we found that the jejunum is the main absorptive site, then the duodenum and ileum. Consequently, a novel micron-size particulate of FD in a core-shell structure was fabricated by a coaxial electrospray technique; within the drug delivery system, Hypromellose K4M (HPMC K4M) was selected as a sheath material to prolong the retention time in the upper GI tract, while povidone K30 (PVP K30) was mixed with FD in the inner layer. The dissolution study in three different media (0.02% Tween-80 solution; phosphate buffer containing 0.02% Tween-80, pH 6.8; and HCl solution containing 0.02% Tween-80, pH 1.2) demonstrated that FD-loaded coaxial electrospray particles (F-COES) could greatly improve the dissolution of FD. Furthermore, in vivo pharmacokinetics revealed that F-COES emerged no changes in the half-life but significantly prolonged the t max and increased the oral bioavailability. Collectively, this work supplies a promising drug release system that will improve the dissolution and enhance the bioavailability simultaneously for those poorly water-soluble drugs mainly absorbed in the upper GI tract.

CAS / MDL: 64-17-5 72509-76-3
研究领域: 药剂学 · 药物递送系统 · 生物药剂学
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SENSORS AND ACTUATORS B-CHEMICAL · 2021 · IF 7.46

Polymeric microsphere enhanced surface plasmon resonance imaging immunosensor for occult blood monitoring

Jie Zhou,Xueliang Wang,Jiajie Chen,Youjun Zeng,Dayong Gu,Bruce Zhi Gao,Yonghong Shao

Occult blood testing is a routine screening method for evaluating the function of the urinary system and digestive tract. The hemoglobin (Hb) content in human excreta is an important indicator of the presence of occult blood. In this study, a surface plasmon resonance imaging (SPRi)-based immunosensor with high sensitivity was developed for the detection of Hb. The immunosensor was constructed by physically immobilizing anti-Hb antibodies on the detection channels. Samples for evaluation were pre-incubated with the polymeric microsphere-antibody conjugate. The shift in resonance wavelength induced by the specific binding of microsphere-antibody-antigen and immobilized antibodies was monitored in real time. Owing to the amplification effect of microspheres, the detection limit of the immunosensor was reduced 42-fold to 4.8 ng/mL under the optimized concentration of immobilized antibody (10 μg/mL) with microsphere-antibody conjugate dilution ratio of 1:200 and incubation time of the microsphere-antibody conjugate and samples (10 min). The immunosensor displayed a good linear response to Hb ranging from 10 ng/mL to 500 ng/mL in both test solutions and in 1:30 urine sample, as well as a good specificity toward Hb and an acceptable recovery rate for spiked Hb solution in urine sample. The immunosensor was also exploited to detect the Hb concentration in 50 clinical urine samples. Therefore, the proposed SPRi immunosensor developed in this study provides a simple, rapid, high-throughput, and sensitive immunology strategy for the detection of occult blood.

研究领域: 生物传感器 · 分析化学 · 医学诊断 · 生物医学工程
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FOOD RESEARCH INTERNATIONAL · 2022 · IF 7.425

Novel carboxymethyl chitosan/N-acetylneuraminic acid hydrogel for the protection of Pediococcus pentosaceus

Yuanfei Ge,Jinyong Wu,Min Pang,Dan Hu,Zhongkui Li,Xiangqin Wang,Lijie Sun,Xiangsong Chen,Jianming Yao

In this study, carboxymethyl chitosan (CMCS) and N - acetylneuraminic acid (NeuAc) were used to develop C-NeuAc hydrogels to encapsulate Pediococcus pentosaceus QK-1. The mechanical properties, thermal stability, in vitro degradation, and pH sensitivity of the hydrogel were evaluated. The C-NeuAc concentration required for optimal hydrogel performance was 3% (w/v). Hydrogel swelling behaviour was effectively assessed by Fickian diffusion and Schott’s second-order kinetic models. The hydrogel demonstrated excellent biocompatibility and low in vitro cytotoxicity. An in vitro assay revealed that the viability of Pediococcus pentosaceus QK-1 in C-NeuAc had decreased by only 1.41 log (CFU/ mL) after exposure to simulated acidic gastric fluid. Moreover, the survival rate of the encapsulated and free Pediococcus pentosaceus QK-1 cells were 80.1% and virtually zero, respectively, after passage through the gastrointestinal tract. It was empirically determined that low temperature and freeze-drying were the ideal condition and method to ensure storage longevity of the hydrogel-encapsulated probiotic. Hence, C-NeuAc hydrogel is highly desirable as a food-grade probiotic delivery vehicle.

研究领域: 生物技术 · 食品科学 · 材料科学
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