JOURNAL OF NANOBIOTECHNOLOGY
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2026
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IF 15
Yanwei Lv,Mengni Jiang,Qiwen Jiang,Xinyuan Zhang,Yijie Xie,Yunyi Yang,Shige Wang,Lianghao Hu,Jiulong Zhao
Pyroptosis is involved in various inflammatory and fibrotic processes, but its specific role in the progression of chronic pancreatitis (CP) remains insufficiently explored. This study first investigated the dynamic expression changes of pyroptosis-related proteins during CP development and verified the regulatory effects of disulfiram (DSF) on key effector cells in CP, namely pancreatic stellate cells (PSCs) and macrophages. Building on these findings, a gut microenvironment-responsive nanoplatform, CuSe/DSF/EL nanoflowers, was designed and synthesized by integrating CuSe (as a carrier and selenium donor), DSF (as the core therapeutic agent), and Eudragit ® L100-55 (EL, a pH-sensitive polymer for intestinal targeting). Results demonstrated that the CuSe/DSF/EL nanoflowers exhibited excellent biocompatibility, robust antioxidant capacity, and efficient electrostatic targeting to inflamed pancreatic tissues via charge interactions. In vivo experiments using a mouse CP model confirmed that the nanoflowers significantly alleviated pancreatic inflammation, fibrosis, and pyroptosis, while effectively repairing pancreatic structure and restoring its function. Further RNA sequencing (RNA-seq) analysis revealed that the nanoflowers reversed CP-associated transcriptomic dysregulation, with a notable focus on correcting impaired pancreatic secretion pathways. This study clarifies the critical role of pyroptosis in CP pathogenesis and provides a novel, multi-mechanistic nanotherapeutic strategy for CP treatment by enhancing the bioavailability and targeting efficiency of DSF.
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DOI
PubMed
高影响因子
International Journal of Pharmaceutics-X
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2025
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IF 6.4
Jie-Zhou,Tian-Le Li,Bo-Wei,Yue-Feng Ruan,Ye-Qin Wang,Jiao-Yan Liu,Meng-Meng Song,Yu-Xian Shen
Midbrain astrocyte-derived neurotrophic factor (MANF) is a secreted protein induced by endoplasmic reticulum stress. Previous studies have indicated that intravenous administration of 1 mg/kg/day recombinant human MANF protein with His tag (His-MANF) for 3 days can ameliorate acute ulcerative colitis in mice. However, long-term intravenous therapy has many disadvantages. In this paper, His-MANF protein was successfully encapsulated into alginate and hyaluronic acid hybrid hydrogel microcapsules in one step using the gas shear method and then coated by Eudragit S100 to construct an oral colon-targeted delivery system (MSH@E). The MSH@E microcapsules exhibited controlled and sustained release behavior and colon-targeting properties. Both fluorescent imaging and immunohistochemistry staining results showed that His-MANF protein could accumulate in the colitis colon for a longer residence time after oral delivery. In vivo studies demonstrated that oral administration of MSH@E microcapsules could alleviate DSS-induced colitis in mice without systemic toxicity. Importantly, even if the oral His-MANF dose was half of the intravenous His-MANF dose, oral delivery was still much more effective than intravenous injection, suggesting the development of the oral colon-targeted delivery system (MSH@E) has great significance and makes a breakthrough from intravenous to oral administration for His-MANF treatment of ulcerative colitis (UC).
研究领域:
药剂学
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胃肠病学
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药物递送系统
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
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2024
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IF 4.8
Dandan Zhang,Hao Wan,Ran Zhao,Yu Zhang,Hong Chen
The therapeutic effect of 5-amino salicylic acid (5-ASA), a first-line therapeutic agent for the treatment of ulcerative colitis (UC), is limited by the modest bioavailability afforded by its oral administration. In this study, a 5-ASA oral delivery system was developed using Eudragit S100-coated iron oxide-chitosan nanocomposites (ES-IOCS/5-ASA) to address this issue. According to drug release studies in vitro, ES-IOCS/5-ASA only released a small amount of drug in simulated gastric fluid with a pH of 1.2. However, in a medium with a pH of 7.5, a relatively rapid and complete release was noted. 5-ASA-loaded iron oxide-chitosan nanocomposites (IOCS/5-ASA) could be effectively taken up by NCM460 cells and performed better anti-inflammatory effects than free 5-ASA. At the same time, IOCS/5-ASA improved barrier damage in DSS-induced NCM460 cells. In vivo models of dextran sulphate sodium (DSS)-induced colitis were used to assess the therapeutic efficacy of oral administration of ES-IOCS/5-ASA. ES-IOCS/5-ASA significantly relieved DSS-induced colitis and enhanced the integrity of the intestinal epithelial barrier. ES-IOCS/5-ASA also reduced the expression of NLRP3, ASC and IL-1β. Additionally, iron oxide nanoparticles used as nanozymes could alleviate inflammation. In summary, this study indicates that ES-IOCS/5-ASA exert anti-inflammatory effects on DSS-induced colitis by improving intestinal barrier function and inhibiting NLRP3 inflammasome expression, presenting a viable therapeutic choice for the treatment of UC.
研究领域:
药学
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纳米技术
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炎症性肠病
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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
JOURNAL OF CONTROLLED RELEASE
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2023
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IF 10.8
Hongbing Liu,Muse Ji,Yuti Bi,Peifu Xiao,Jiansong Zhao,Jingxin Gou,Tian Yin,Haibing He,Huaiwei Ding,Xing Tang,Yu Zhang
Excessive reactive oxygen species (ROS) and stressed inflammatory response are major characteristics of ulcerative colitis , which cause disease progression and aggravation. Herein, a novel mesoporous cerium oxide nanozymes (MCN) was designed and then loaded with Myeloid differentiation factor-88 (MyD88) inhibitor for synergistic treatment of colitis by scavenging ROS and regulating inflammation. This innovative MCN with average particle size of 200.7 nm , specific surface area of 119.78 m 2 /g and mesopores of 4.47 nm not only exhibited excellent SOD-like and CAT-like activities to scavenge ROS but also could act as a carrier to load MyD88 inhibitor, TJ-M2010–5, (abbreviated as TJ-5) into their mesopores, achieving the effect of ‘two birds with one stone’. Besides, the modification of dextran sulfate sodium (TJ-5/MCN/DSS) increased the internalization of nanozymes into activated macrophages and enhanced in vitro anti-inflammatory ability. To enhance colon targeting, we coated TJ-5/MCN/DSS with the enteric material Eudragit S100 , preventing premature release or absorption of the drug in the gastrointestinal tract after oral administration. The results demonstrated that TJ-5/MCN/DSS/Eudragit not only achieved delayed drug release and improved colon targeting but also exhibited optimal therapeutic efficacy in colitis mice. Mechanistically, the MCN-mediated ROS scavenging and TJ-5-mediated MyD88 blockade synergistically inhibited the NF-κB signaling pathway, thereby reducing the inflammatory response. Importantly, TJ-5/MCN/DSS/Eudragit did not induce systemic toxicity. In conclusion, our work not only presents a novel carrier capable of scavenging ROS but also provides proof of concept for the synergistic treatment of colitis using this carrier in combination with MyD88 inhibitors. This study proposes a safe and efficient strategy for targeting ROS-associated inflammation.
研究领域:
药学
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纳米技术
·
炎症性肠病
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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
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