Advanced Healthcare Materials
·
2025
·
IF 9.6
Yanxue Si,Ruitao Cha,Pai Zhang,Fengshan Zhou,Wenbing Yuan,Xingyu Jiang
5-Aminosalicylic acid (5-ASA) is the first-line drug for ulcerative colitis (UC), which encounters therapeutic constraints due to the poor water solubility and absorption by the upper gastrointestinal. Here, a cyclodextrin-based metal-organic framework (CD-MOF) is used as a carrier for 5-ASA (ASA@CM) to enhance its solubility. To improve the targeted release 5-ASA, ASA@CM is incorporated into sodium alginate/ L -arginine complex (SA-LA) to obtain the desired microspheres (ASA@CM/SL) by electrospray. ASA@CM/SL safeguards 5-ASA against the harsh gastrointestinal environment and provides favorable delivery to the colon. The anti-inflammatory and anti-oxidant activity is studied by measuring inflammatory factors and reactive oxygen species (ROS). The therapeutic effect of ASA@CM/SL on UC mice induced with dextran sulfate sodium is assessed. The biosafety by evaluating cytotoxicity and organ toxicity is studied. ASA@CM/SL shows excellent therapeutic effects for UC, as evidenced by its alleviation of inflammatory response and restoration of disrupted intestinal barriers. ASA@CM/SL features low cytotoxicity and low organ toxicity. This study provides a potential strategy for improving 5-ASA solubility and delivery efficiency, which may also be applied to broadly tackle various small hydrophobic molecules to treat UC and other intestinal diseases.
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PubMed
高影响因子
STARCH-STARKE
·
2021
·
IF 2.741
Qiujie Fang,Na Chen,Shan Hu,Sheng Hu,Jianfeng Ye,Xiaozhou Ye,Yun Wang
Some special oral drugs may cause adverse reactions and degrade in the stomach; therefore, it is necessary to develop a new generation of multifunctional drug delivery carries to deal with such issues. Herein, by polyelectrolyte composite method using KGM and CS as raw material, CKGM/CS/TPP/5-ASA microcapsules are prepared using 5-ASA as model drug, and then coated with an acid-resistant polyacrylic acid polymer layer. The size of CKGM/CS/TPP/5-ASA microcapsules is relatively uniform, with average particle size 1.78 ± 0.02 mm. The inner part of microcapsules has a core-shell three-dimensional network structure, and the 5-ASA embedded in the network is in its crystal form. The microcapsules exhibited good encapsulate properties, with 495.5 µg mg −1 drug loading amount and 82.3% encapsulation efficiency under optimized conditions. The in vitro release properties of microcapsules are also studied, and results showed that the drug is released little in Simulated Gastric Fluid solution (pH 1.2) but fully released in Simulated Colonic Fluid or Phosphate Buffered Solution (pH 7.0), and the release rate is higher in SCF solution, indicating that β-mannanase could facilitate release. All these results indicated that CKGM/CS/TPP microcapsules have good pH-controlled release, enzymatic release, and sustained release properties, hence they are promising multifunctional colon-targeted release carriers.
研究领域:
药学
·
生物材料学
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DOI
高影响因子
PHARMACEUTICAL RESEARCH
·
2021
·Vol. 38
·期 4
·693-706
·
IF 4.2
Xu Wenhao,Su Wenjing,Xue Zhencheng,Pu Faxiang,Xie Zhangfu,Jin Kongliang,Polyakov Nikolay E.,Dushkin Alexander V.,Su Weike
Purpose This study aims to overcome the challenges of the current oral targeted drug delivery system, such as the complex preparation process, poor biocompatibility, and delayed drug release. Methods Here, a non-covalent polymer hydrogel was prepared using the mechanochemical method, and the solid phase loading of 5-amino salicylic acid (5-ASA) was realized. Results The results obtained from the thermodynamics study, particle size analysis, and electron microscopy show that chitosan (CS) and sodium alginate (SA) form a pH-sensitive hydrogel under the mechanochemical force and also maintain good stability in aqueous solution. Fluorescent tracers study showed that the pH-sensitive hydrogel could achieve the targeted drug release in the colon and the retention time was over 12 h. Next, in vivo efficacy studies, change in mice body weight, DAI (disease activity index) score, thymus, and spleen index, and the diseased state of the mice colon revealed that the pH-sensitive hydrogel is an improved drug delivery system over 5-ASA API commercial preparations as observed in the efficacy and toxicological studies. Conclusion This method uses an innovative preparation technology that without the need of cross-linking agent to produce an efficient colon-targeted drug delivery system for the treatment of ulcerative colitis.
研究领域:
药剂学
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生物技术
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药物递送系统
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PubMed
高影响因子
CHEMICAL ENGINEERING SCIENCE
·
2026
·
IF 5.1
Shuang Liu,Lei Ye,Shaokai Huang,Peng Zhou,Mingxuan Ma,Miao Hu,Xujin Ren,Xin Pu,Xin Han,Jichang Liu
La/ZSM-5@ASA composites were developed by a stepwise assembly strategy. • La 3+ displaced the acidic protons and generated new BAS [Si-OLa(OH) 2 -Al]. • ASA overcoat passivated external surface acid sites and enabled pre-cracking. • Hierarchical La/ZSM-5@ASA shows high light-olefin selectivity in n -paraffin cracking. Catalytic cracking of surplus automotive fuels, heavy oil and waste plastics into light olefins is an efficient resource-reutilization strategy. Conventional ZSM-5 zeolites, however, suffer from limited light-olefin selectivity and coke-induced deactivation due to strong acidity and microporous constraints. Herein, a stepwise assembly strategy involving La modification and subsequent amorphous silica-alumina (ASA) overcoating was developed to construct core–shell catalysts with optimized acidity and diffusion. La modification modulated acid strength and distribution, and DFT calculations revealed it lowered the energy barrier of the rate-determining protonation step, promoting propylene formation. The ASA overcoat, applied via co-gelation, passivated external strong Brønsted acid sites and introduced open interfacial diffusion channels. This architecture enabled pre-cracking of reactants, promoting efficient C-C bond cleavage and suppressing secondary reactions. The optimized hierarchical La/ZSM-5@ASA(1:1) achieved 63.10% total ethylene and propylene selectivity in n -heptane cracking, outperforming ZSM-5 and 0.50La/ZSM-5 by 5.12% and 1.38%, respectively. This advantage is more pronounced for longer linear hydrocarbons, and the suppression of methane and coke precursors boosts atom utilization efficiency, indicating a carbon-economic cracking pathway.
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高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2026
·
IF 5.9
Weiguang Su,Jianbin Liang,Dawei Wang,Siegfried Yeboah,Jiemeng Ding,Tian Lan,Ruirui Zhang,Qing Xu,Li Wang
Monodisperse 5-ASA microcapsules (CV < 3%) are engineered via microfluidics. • Nanocrystal-in-microcapsule architecture yields high drug loading (20.4 wt%). • pH 6.1 threshold enables release in the acidic IBD microenvironment. • Moving-boundary kinetics map single-particle to macro-scale release. The performance of targeted oral delivery systems for hydrophobic drugs like 5-aminosalicylic acid is limited by variable release kinetics and premature release in the upper gastrointestinal tract. To address this challenge, monodisperse 5-aminosalicylic acid nanocrystal-in-hydroxypropyl methylcellulose acetate succinate (5-ASA NCs@HPMCAS) composite microcapsules were prepared via microfluidic interfacial assembly and antisolvent precipitation. Droplet-templated solidification yielded microcapsules with an average diameter of 28.33 μm, a coefficient of variation < 3%, a drug loading of 20.4 wt% and an encapsulation efficiency of 83.3%. Driven by the pH-dependent transition of the HPMCAS shell, the microcapsules remained structurally intact under simulated gastric and proximal intestinal conditions (pH < 6.0) but underwent rapid interfacial erosion around pH 6.1. The model payload was released within approximately 3 min at pH 7.2 under quiescent in vitro conditions, while 5-ASA release reached 88.5% at pH 6.5 over 4 h. Ex vivo GI imaging of DiR-labeled microcapsules provided preliminary evidence of upper-GI retention and lower-GI localization after oral administration. Residual ethyl acetate was approximately 217 ppm, while dimethyl sulfoxide was below the assay’s quantification range. A 24-hour Caco-2 assay showed cell viability above 90%, supporting preliminary in vitro cytocompatibility under the tested conditions. The uniform particle size also enabled comparison between single-particle moving-boundary kinetics and macroscopic release behavior, providing a physicochemical basis for pH-responsive oral delivery.
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高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Rongjiao Sun,Limei Zhu,Xianzhu You,Rong Chen,Jiante Li,Rongrong Pan,Yueqi Jin,Hua Zhou,Ying Tan,Jiajia Dong,Wanle Hu
5-Aminosalicylic acid (5-ASA) is widely used in the clinical treatment of ulcerative colitis (UC), but its effectiveness is limited by poor patient compliance and inadequate drug retention. Herein, a novel thermoresponsive nanogel (P(NVCL-co-GelMA)) was synthesized through the copolymerization of N-vinylcaprolactam (NVCL) and methacrylated gelatin (GelMA). This nanogel serves as an effective carrier for 5-ASA, transitioning from a sol to a hydrogel at physiological temperatures, thereby enhancing drug retention and reducing leakage. In vitro studies revealed that the nanogel has a lower critical solution temperature of approximately 34 °C and can form a gel within 60 s. It demonstrates superior bioadhesion, biocompatibility, and controlled release of 5-ASA. In a rat model of UC, the 5-ASA-loaded nanogel significantly improved weight loss and disease activity index scores compared to untreated rats. The hydrogel coating acts as a biophysical barrier on the intestinal mucosa, effectively blocking the irritation caused by metabolites and maximizing the therapeutic effect, comparable to that of commercial mesalazine enema (Salofalk). The P(NVCL-co-GelMA) nanogel represents a promising drug delivery system for the treatment of UC, offering extended drug retention, reduced leakage, and enhanced therapeutic efficacy.
研究领域:
药学
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药物递送系统
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结直肠疾病
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高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2023
·Vol. 21
·期 1
·1-19
·
IF 10.2
Qiu Lei,Shen Renbin,Wei Lei,Xu Shujuan,Xia Wei,Hou Yan,Cui Jinxin,Qu Rong,Luo Jiale,Cao Jian,Yang Jie,Sun Jing,Ma Ronglin,Yu Qiang
Patients with inflammatory bowel disease (IBD) always suffer from severe abdominal pain and appear to be at high risk for colorectal cancer. Recently, the co-delivery of targeted drugs and gut microbiota has developed into an attractive strategy. A new strategy using gut microbiota fermentation to overcome the interspace diffuse resistance from the mucus layer to control drug release in inflammatory bowel sites (IBS sites) has not yet been available. Here, we designed an alginate hydrogel microsphere encapsulating bifidobacterium (Bac) and drug-modified nanoscale dietary fibers (NDFs). The hydrogel microsphere is responsible for protecting drugs from acidic and multi-enzymatic environments and delivering drugs to the colorectum. Subsequently, the fermentation of Bac by digesting NDFs and proteins as carbon and nitrogen sources can promote drug release and play a probiotic role in the gut microbiota. In vitro evidence indicated that small-sized NDF (NDF-1) could significantly promote short-chain fatty acid (SCFA) expression. Notably, NDF-1 hydrogel microspheres showed a boost release of 5-ASA in the IBS sites, resulting in the amelioration of gut inflammation and remodeling of gut microbiota in chronic colitis mice. This study developed a controlled release system based on microbial fermentation for the treatment of IBD.
研究领域:
药学
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生物技术
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胃肠病学
·
微生物学
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PubMed
高影响因子
Iranian Journal of Basic Medical Sciences
·
2019
·
IF 1.854
Yan Yan,Fengling Ren,Pengchong Wang,Ying Sun,Jianfeng Xing
Objective(s): This study is aimed to design and synthesize a prodrug of 5-aminosalicylic acid and evaluate its ameliorative effect on experimental ulcerative colitis (UC). Materials and Methods: 5-Aminosalicylic acid-alanine (5-ASA-ALA) was synthesized and characterized. Its stability study was conducted in rat plasma and in the gastrointestinal tract environment, its transport characteristic was assessed using the Caco-2 cells. Its colon-targeting property was evaluated by the pharmacokinetic study, and incubation studies. A series of indicators were used to investigate its therapeutic effect on experimental colitis, including the survival rate and body weight of mice, the disease activity index (DAI), the colonic damage score and colon index, the myeloperoxidase (MPO) activity and the levels of malondialdehyde (MDA), total superoxide dismutase (SOD), glutathione (GSH) and glutathione peroxidase (GSH-Px) in colonic tissues. Results: 5-ASA-ALA was barely absorbed in the Caco-2 monolayer or into the rat blood. It was remarkably stable when incubated in the upper gastrointestinal tract, while gradually hydrolyzed in the colon of rats. When orally administered to mice, 5-ASA-ALA had significantly greater therapeutic effect on colitis than the positive control. Conclusion: 5-ASA-ALA is demonstrated to be a promising oral colon-targeting prodrug of 5-ASA and has potential application in UC treatment.
研究领域:
药物学
·
胃肠病学
·
药物开发
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DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2024
·
IF 5.7
Hanhan Xie,Ji Yang,Tong Liu,Xinyue Zhang,Shan Zuo,Yingjie Gao,Xi Kuang,Tao Zhang
Lignin is dietary fiber from plant cell walls with multiple biological antioxidant and anti-inflammatory activities. However, whether lignin protects from ulcerative colitis (UC) and underlying mechanisms is unclear. Herein, UC mouse modeling was established with dextran sulfate sodium (DSS) and treatment with lignin for 1 week. Results showed that lignin inhibited the disease activity index (DAI), histological damage, and cell death in UC mice. We also found that lignin reversed the alterations of ferroptotic features in DSS-induced mice and ferroptotic cells, as evidenced by increased expression of GPX4 and 4-HNE and decreased transferrin expression, ameliorating the phenomenon of iron overload, GSH depletion, and ROS and MDA production. Furthermore, the increased expression of NRF2 was observed in IECs under lignin treatment. Also, the upstream regulatory molecule ERK of NRF2 was activated. Further research revealed that lignin can bind GPR37. Meanwhile, lignin was able to alleviate colitis by improving the composition of the intestinal flora in DSS mice and its effect was similar to that of 5-ASA. Taken together, these findings suggest that lignin protects against ferroptosis in UC by combining GPR37 and activating the ERK-NRF2-GPX4 signaling axis, which provides new ideas for clinical intervention in the treatment of UC.
研究领域:
胃肠病学
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药理学
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分子生物学
·
免疫学
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DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）